Breast and Cervical Cancer Screenings: A Systematic Economic Review of Patient Navigation Services.

INTRODUCTION: This paper examined the economic evidence of patient navigation services to increase breast and cervical cancer screenings among historically disadvantaged racial and ethnic populations and people with lower incomes. METHODS: The literature search strategy for this systematic review included English-language studies conducted in high-income countries that were published from database inception to December 2022. Studies on patients with existing cancer or without healthcare system involvement were excluded. Analysis was completed in January 2023. All monetary values reported are in 2022 U.S. dollars. RESULTS: The search yielded 3 breast cancer, 2 cervical cancer, and 2 multiple cancer studies that combined breast and cervical cancer with other cancer screenings. For breast cancer screening, the intervention cost per person ranged from $109 to $10,245. Two studies reported $154 and $740 as intervention cost per additional person screened. Changes in healthcare cost per person from 2 studies were $202 and $2,437. Two studies reported cost per quality-adjusted life year (QALY) gained of $3,852 and $39,159 while one study reported cost per life year (LY) gained of $22,889. For cervical cancer, 2 studies reported intervention cost per person ($103 and $794) and per additional person screened ($56 and $533) with one study reporting a cost per QALY gained ($924). DISCUSSION: All estimates of cost per QALY/LY saved for breast cancer screening were below a conservative threshold of $50,000 indicating that patient navigation services for breast cancer screening were cost-effective. There is limited evidence to determine cost-effectiveness of patient navigation services for cervical cancer screening.

Application of Near-Infrared Spectroscopy for Screening of Chlorothiazide Sodium Vials.

Chlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide. Chlorothiazide sodium has a molecular weight of 317.71 amu. Since 2020 there have been multiple national shortages of chlorothiazide. Recent studies target chlorothiazide's low bioavailability, aiming to enhance it through nanoparticle production via a supercritical method. The drug's solubility in supercritical carbon dioxide (scCO2) is vital, with measurements ranging from 0.417×10-5 to 1.012×10-5 mole fraction under specific conditions. Adding co-solvents, like ethanol, DMSO, and acetone, to scCO2 boosts solubility, with ethanol proving most effective, enhancing solubility by 2.02-11.75 times. Intra-lot variability was discovered in a sample of a lot of chlorothiazide sodium by the University of Kentucky Drug Quality Task Force. Two vials of six screened in one lot were displaced from the center of the lot by 4.0 and 4.2 SDs, respectively. Inter-lot variability was confirmed in the near-IR spectra of 204 vials obtained from 28 different lots of chlorothiazide sodium. Using full spectrum BEST analysis 13 vials (6.4%) were outliers.

Parks, Trails, and Greenways for Physical Activity: A Community Guide Systematic Economic Review.

INTRODUCTION: This systematic economic review examined the cost-benefit and cost-effectiveness of park, trail, and greenway infrastructure interventions to increase physical activity or infrastructure use. METHODS: The search period covered the date of inception of publications databases through February 2022. Inclusion was limited to studies that reported cost-benefit or cost-effectiveness outcomes and were based in the U.S. and other high-income countries. Analyses were conducted from March 2022 through December 2022. All monetary values reported are in 2021 U.S. dollars. RESULTS: The search yielded 1 study based in the U.S. and 7 based in other high-income countries, with 1 reporting cost-effectiveness and 7 reporting cost-benefit outcomes. The cost-effectiveness study based in the United Kingdom reported $23,254 per disability-adjusted life year averted. The median benefit-to-cost ratio was 3.1 (interquartile interval=2.9-3.9) on the basis of 7 studies. DISCUSSION: The evidence shows that economic benefits exceed the intervention cost of park, trail, and greenway infrastructure. Given large differences in the size of infrastructure, intervention costs and economic benefits varied substantially across studies. There was insufficient number of studies to determine the cost-effectiveness of these interventions.

Screening for quality with process analytical technology in a health-system pharmacy: A primer.

PURPOSE: The University of Kentucky Drug Quality Study team briefly reviews the growing concerns over pharmaceutical manufacturing quality in the globalized environment, reviews the historical approach by the US Food and Drug Administration (FDA) that prioritizes process over product in enforcing quality with manufacturers, reviews the science of process analytical technology (PAT) such as near-infrared (NIR) spectroscopy, illustrates the use of PAT methods for assessing uniformity and quality in injectable pharmaceuticals, and demonstrates the application of NIR spectroscopy in a health-system pharmacy setting while maintaining current good practice quality guidelines and regulations (cGxP). SUMMARY: Given that the current approach to monitoring quality in pharmaceutical manufacturing was developed in the late 1960s at a time when manufacturing was mostly domestic, the current approach prioritizes process over product, and the global footprint of manufacturing is straining federal resources to fulfill their task of monitoring quality, an approach to augment the quality monitoring process has been developed. PAT methodologies are supported by FDA for monitoring quality and offer a fast, low-cost, nondestructive solution. Given that the Accreditation Council for Pharmacy Education has not required qualitative/quantitative analysis and drug assaying in the pharmacy curriculum for several decades, the authors spend time explaining the science behind one of these PAT methodologies, NIR spectroscopy. This primer reviews the application of this technology in the health-system pharmacy setting and the relevant clinical applications. CONCLUSION: Utilizing PAT methodologies such as NIR spectroscopy, health-system pharmacies can gain insights about whether process controls are in place or lacking in FDA-approved formulations.

Implementation of a medication delivery service for ambulatory oncology infusion patients.

OBJECTIVE: Patients receiving infusions for the treatment of cancer are commonly prescribed supportive care medications which are filled through retail pharmacies. The initial phase of the COVID-19 pandemic created hurdles for patients to receive supportive care medications due to concerns related to exposure risk. Meds-to-Chemo Chairs (M2CC) was created allowing an onsite retail pharmacy to dispense and hand-deliver supportive care prescriptions to patients in the infusion suite. The purpose of this study was to assess the value of this program. DATA SOURCES: The volume of prescriptions dispensed through the M2CC service, as well as the financial impact, was tracked through the prescription software system used by the onsite retail pharmacy dispensing and delivering the medications. DATA SUMMARY: Through the first 2.5 years of the program, M2CC has delivered over 13,000 prescriptions with an estimated gross revenue of $3.5 million. CONCLUSIONS: The M2CC medication delivery program has proved to be highly successful and feasible.

Economics of Team-Based Care for Blood Pressure Control: Updated Community Guide Systematic Review.

INTRODUCTION: This paper examined the recent evidence from economic evaluations of team-based care for controlling high blood pressure. METHODS: The search covered studies published from January 2011 through January 2021 and was limited to those based in the U.S. and other high-income countries. This yielded 35 studies: 23 based in the U.S. and 12 based in other high-income countries. Analyses were conducted from May 2021 through February 2023. All monetary values reported are in 2020 U.S. dollars. RESULTS: The median intervention cost per patient per year was $438 for U.S. studies and $299 for all studies. The median change in healthcare cost per patient per year after the intervention was -$140 for both U.S. studies and for all studies. The median net cost per patient per year was $439 for U.S. studies and $133 for all studies. The median cost per quality-adjusted life year gained was $12,897 for U.S. studies and $15,202 for all studies, which are below a conservative benchmark of $50,000 for cost-effectiveness. DISCUSSION: Intervention cost and net cost were higher in the U.S. than in other high-income countries. Healthcare cost averted did not exceed intervention cost in most studies. The evidence shows that team-based care for blood pressure control is cost-effective, reaffirming the favorable cost-effectiveness conclusion reached in the 2015 systematic review.

Efficacy of Do-It-Yourself air filtration units in reducing exposure to simulated respiratory aerosols.

Many respiratory diseases, including COVID-19, can be spread by aerosols expelled by infected people when they cough, talk, sing, or exhale. Exposure to these aerosols indoors can be reduced by portable air filtration units (air cleaners). Homemade or Do-It-Yourself (DIY) air filtration units are a popular alternative to commercially produced devices, but performance data is limited. Our study used a speaker-audience model to examine the efficacy of two popular types of DIY air filtration units, the Corsi-Rosenthal cube and a modified Ford air filtration unit, in reducing exposure to simulated respiratory aerosols within a mock classroom. Experiments were conducted using four breathing simulators at different locations in the room, one acting as the respiratory aerosol source and three as recipients. Optical particle spectrometers monitored simulated respiratory aerosol particles (0.3-3 µm) as they dispersed throughout the room. Using two DIY cubes (in the front and back of the room) increased the air change rate as much as 12.4 over room ventilation, depending on filter thickness and fan airflow. Using multiple linear regression, each unit increase of air change reduced exposure by 10%. Increasing the number of filters, filter thickness, and fan airflow significantly enhanced the air change rate, which resulted in exposure reductions of up to 73%. Our results show DIY air filtration units can be an effective means of reducing aerosol exposure. However, they also show performance of DIY units can vary considerably depending upon their design, construction, and positioning, and users should be mindful of these limitations.

Assessment of Vecuronium Quality Using Near-Infrared Spectrometry.

This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot. Several outliers in the spectral data suggested potential differences in the chemical composition or sample condition of the vials. The outliers were identified and their spectral features were examined. A total of eight unique outliers were found in the PC space from PCs 1 to 9, so 22% of the total vials were outliers. The study findings suggest that the manufacturing process of vecuronium bromide may have been operating outside of a state of process control. Further investigation is needed to determine the source of these variations and their impact on the safety and efficacy of the drug product.

Development of an automated liquid biopsy assay for methylated markers in advanced breast cancer.

Current molecular liquid biopsy assays to detect recurrence or monitor response to treatment require sophisticated technology, highly trained personnel, and a turnaround time of weeks. We describe the development and technical validation of an automated Liquid Biopsy for Breast Cancer Methylation (LBx-BCM) prototype, a DNA methylation detection cartridge assay that is simple to perform and quantitatively detects nine methylated markers within 4.5 h. LBx-BCM demonstrated high interassay reproducibility when analyzing exogenous methylated DNA (75-300 DNA copies) spiked into plasma (Coefficient of Variation, CV = 7.1 - 10.9%) and serum (CV = 19.1 - 36.1%). It also demonstrated high interuser reproducibility (Spearman r = 0.887, P < 0.0001) when samples of metastatic breast cancer (MBC, N = 11) and normal control (N = 4) were evaluated independently by two users. Analyses of interplatform reproducibility indicated very high concordance between LBx-BCM and the reference assay, cMethDNA, among 66 paired plasma samples (MBC N = 40, controls N = 26; Spearman r = 0.891; 95% CI = 0.825 - 0.933, P< 0.0001). LBx-BCM achieved a ROC AUC = 0.909 (95% CI = 0.836 - 0.982), 83% sensitivity and 92% specificity; cMethDNA achieved a ROC AUC = 0.896 (95% CI = 0.817 - 0.974), 83% sensitivity and 92% specificity in test set samples. The automated LBx-BCM cartridge prototype is fast, with performance levels equivalent to the highly sensitive, manual cMethDNA method. Future prospective clinical studies will evaluate LBx-BCM detection sensitivity and its ability to monitor therapeutic response during treatment for advanced breast cancer.

Biological effects of inhaled crude oil vapor. II. Pulmonary effects.

Workers involved in oil exploration and production in the upstream petroleum industry are exposed to crude oil vapor (COV). COV levels in the proximity of workers during production tank gauging and opening of thief hatches can exceed regulatory standards, and several deaths have occurred after opening thief hatches. There is a paucity of information regarding the effects of COV inhalation in the lung. To address these knowledge gaps, the present hazard identification study was undertaken to investigate the effects of an acute, single inhalation exposure (6 h) or a 28 d sub-chronic exposure (6 h/d × 4 d/wk × 4 wks) to COV (300 ppm; Macondo well surrogate oil) on ventilatory and non-ventilatory functions of the lung in a rat model 1 and 28 d after acute exposure, and 1, 28 and 90 d following sub-chronic exposure. Basal airway resistance was increased 90 d post-sub-chronic exposure, but reactivity to methacholine (MCh) was unaffected. In the isolated, perfused trachea preparation the inhibitory effect of the airway epithelium on reactivity to MCh was increased at 90 d post-exposure. Efferent cholinergic nerve activity regulating airway smooth muscle was unaffected by COV exposure. Acute exposure did not affect basal airway epithelial ion transport, but 28 d after sub-chronic exposure alterations in active (Na+ and Cl¯) and passive ion transport occurred. COV treatment did not affect lung vascular permeability. The findings indicate that acute and sub-chronic COV inhalation does not appreciably affect ventilatory properties of the rat, but transient changes in airway epithelium occur.

FDA Approaches in Monitoring Drug Quality, Forces Impacting the Drug Quality, and Recent Alternative Strategies to Assess Quality in the US Drug Supply.

Since the US Food and Drug Administration (FDA) began monitoring the quality of pharmaceutical manufacturing by enforcing current good manufacturing practices roughly 60 years ago, forces related to the global economy have changed, rendering the task of monitoring quality more difficult. Alternative strategies by groups like Valisure, LLC, and the University of Kentucky Drug Quality Study to monitor the quality of the currently circulated US drug supply through end-product testing and screening have resulted in several concerning findings. Given the successful approaches of identifying quality defects in pharmaceuticals by non-regulatory bodies, and considering the changing landscape and pressures on manufacturing, the FDA, large buying groups, and the US Department of Defense should consider these alternative strategies as a means to augment current regulatory activities.

Reduction of exposure to simulated respiratory aerosols using ventilation, physical distancing, and universal masking.

To limit community spread of SARS-CoV-2, CDC recommends universal masking indoors, maintaining 1.8 m of physical distancing, adequate ventilation, and avoiding crowded indoor spaces. Several studies have examined the independent influence of each control strategy in mitigating transmission in isolation, yet controls are often implemented concomitantly within an indoor environment. To address the influence of physical distancing, universal masking, and ventilation on very fine respiratory droplets and aerosol particle exposure, a simulator that coughed and exhaled aerosols (the source) and a second breathing simulator (the recipient) were placed in an exposure chamber. When controlling for the other two mitigation strategies, universal masking with 3-ply cotton masks reduced exposure to 0.3-3 µm coughed and exhaled aerosol particles by >77% compared to unmasked tests, whereas physical distancing (0.9 or 1.8 m) significantly changed exposure to cough but not exhaled aerosols. The effectiveness of ventilation depended upon the respiratory activity, that is, coughing or breathing, as well as the duration of exposure time. Our results demonstrate that a layered mitigation strategy approach of administrative and engineering controls can reduce personal inhalation exposure to potentially infectious very fine respiratory droplets and aerosol particles within an indoor environment.

Olaparib Use in Patients With Metastatic Breast Cancer Harboring Somatic BRCA1/2 Mutations or Mutations in Non-BRCA1/2, DNA Damage Repair Genes.

BACKGROUND: Poly-ADP ribose polymerase (PARP) inhibitors (PARPi) are active in patients with germline BRCA1/2 (gBRCA1/2)-mutated breast cancer, accounting for 5% to 10% of all breast cancers. Another 5% to 10% harbor somatic BRCA1/2 (sBRCA1/2) mutations or mutations in non-BRCA1/2, homologous recombination repair (HRR) genes but until recently, there were no data for the use of PARPi in these patients. This study examines the use of olaparib in patients with metastatic breast cancer harboring sBRCA1/2 or germline or somatic non-BRCA1/2, HRR mutations and demonstrates potential activity of PARPi in this setting. METHODS: In this retrospective, single institution study, patients who were treated with off-label, off-protocol olaparib for metastatic breast cancer harboring sBRCA1/2 or germline or somatic non-BRCA1/2, HRR mutations were identified. The primary aim was to describe these patients' demographics, tumor characteristics, mutations, safety and tolerability, response rates, progression free survival, PARPi-associated survival and subsequent treatment. RESULTS: Seven patients were treated off-label, off-trial with olaparib for sBRCA1/2-mutated cancers (n = 4) or non-BRCA1/2, HRR-mutated cancers (n = 3). All patients with sBRCA1/2-mutated cancers responded to PARP inhibition; patients with non-BRCA1/2, HRR-mutated cancers did not respond. The median progression free survival in patients with a sBRCA1/2 mutation was 6.5 months (range 5-9 months) vs. 3 months (range 2-4 months) in patients with non-BRCA1/2, HRR mutations. CONCLUSION: This single institution experience adds to recent larger reports confirming evidence for PARPi therapy in patients with metastatic breast cancer harboring sBRCA1/2 mutations. No activity was observed in patients with either germline or somatic non-BRCA1/2, HRR-mutated cancers.

Systematic Review of Self-Measured Blood Pressure Monitoring With Support: Intervention Effectiveness and Cost.

INTRODUCTION: Self-measured blood pressure monitoring with support is an evidence-based intervention that helps patients control their blood pressure. This systematic economic review describes how certain intervention aspects contribute to effectiveness, intervention cost, and intervention cost per unit of the effectiveness of self-measured blood pressure monitoring with support. METHODS: Papers published between data inception and March 2021 were identified from a database search and manual searches. Papers were included if they focused on self-measured blood pressure monitoring with support and reported blood pressure change and intervention cost. Papers focused on preeclampsia, kidney disease, or drug efficacy were excluded. Quality of estimates was assessed for effectiveness, cost, and cost per unit of effectiveness. Patient characteristics and intervention features were analyzed in 2021 to determine how they impacted effectiveness, intervention cost, and intervention cost per unit of effectiveness. RESULTS: A total of 22 studies were included in this review from papers identified in the search. Type of support was not associated with differences in cost and cost per unit of effectiveness. Lower cost and cost per unit of effectiveness were achieved with simple technologies such as interactive phone systems, smartphones, and websites and where providers interacted with patients only as needed. DISCUSSION: Some of the included studies provided only limited information on key outcomes of interest to this review. However, the strength of this review is the systematic collection and synthesis of evidence that revealed the associations between the characteristics of implemented interventions and their patients and the interventions' effectiveness and cost, a useful contribution to the fields of both research and implementation.

Pharmacist Interventions for Medication Adherence: Community Guide Economic Reviews for Cardiovascular Disease.

INTRODUCTION: Adherence to medications for cardiovascular disease and its risk factors is less than optimal, although greater adherence to medication has been shown to reduce the risk factors for cardiovascular disease. This paper examines the economics of tailored pharmacy interventions to improve medication adherence for cardiovascular disease prevention and management. METHODS: Literature from inception of databases to May 2019 was searched, yielding 29 studies for cardiovascular disease prevention and 9 studies for cardiovascular disease management. Analyses were done from June 2019 through May 2020. All monetary values are in 2019 U.S. dollars. RESULTS: The median intervention cost per patient per year was $246 for cardiovascular disease prevention and $292 for cardiovascular disease management. The median change in healthcare cost per person per year due to the intervention was -$355 for cardiovascular disease prevention and -$2,430 for cardiovascular disease management. The median total cost per person per year was -$89 for cardiovascular disease prevention, with a median return on investment of 0.01. The median total cost per person per year for cardiovascular disease management was -$1,080, with a median return on investment of 7.52, and 6 of 7 estimates indicating reduced healthcare cost averted exceeded intervention cost. For cardiovascular disease prevention, the median cost per quality-adjusted life year gained was $11,298. There were no cost effectiveness studies for cardiovascular disease management. DISCUSSION: The evidence shows that tailored pharmacy-based interventions to improve medication adherence are cost effective for cardiovascular disease prevention. For cardiovascular disease management, healthcare cost averted exceeds the cost of implementation for a favorable return on investment from a healthcare systems perspective.

Efficacy of Ventilation, HEPA Air Cleaners, Universal Masking, and Physical Distancing for Reducing Exposure to Simulated Exhaled Aerosols in a Meeting Room.

There is strong evidence associating the indoor environment with transmission of SARS-CoV-2, the virus that causes COVID-19. SARS-CoV-2 can spread by exposure to droplets and very fine aerosol particles from respiratory fluids that are released by infected persons. Layered mitigation strategies, including but not limited to maintaining physical distancing, adequate ventilation, universal masking, avoiding overcrowding, and vaccination, have shown to be effective in reducing the spread of SARS-CoV-2 within the indoor environment. Here, we examine the effect of mitigation strategies on reducing the risk of exposure to simulated respiratory aerosol particles within a classroom-style meeting room. To quantify exposure of uninfected individuals (Recipients), surrogate respiratory aerosol particles were generated by a breathing simulator with a headform (Source) that mimicked breath exhalations. Recipients, represented by three breathing simulators with manikin headforms, were placed in a meeting room and affixed with optical particle counters to measure 0.3-3 µm aerosol particles. Universal masking of all breathing simulators with a 3-ply cotton mask reduced aerosol exposure by 50% or more compared to scenarios with simulators unmasked. While evaluating the effect of Source placement, Recipients had the highest exposure at 0.9 m in a face-to-face orientation. Ventilation reduced exposure by approximately 5% per unit increase in air change per hour (ACH), irrespective of whether increases in ACH were by the HVAC system or portable HEPA air cleaners. The results demonstrate that mitigation strategies, such as universal masking and increasing ventilation, reduce personal exposure to respiratory aerosols within a meeting room. While universal masking remains a key component of a layered mitigation strategy of exposure reduction, increasing ventilation via system HVAC or portable HEPA air cleaners further reduces exposure.

Efficacy of universal masking for source control and personal protection from simulated cough and exhaled aerosols in a room.

Face masks reduce the expulsion of respiratory aerosols produced during coughs and exhalations ("source control"). Factors such as the directions in which people are facing (orientation) and separation distance also affect aerosol dispersion. However, it is not clear how the combined effects of masking, orientation, and distance affect the exposure of individuals to respiratory aerosols in indoor spaces. We placed a respiratory aerosol simulator ("source") and a breathing simulator ("recipient") in a 3 m × 3 m chamber and measured aerosol concentrations for different combinations of masking, orientation, and separation distance. When the simulators were front-to-front during coughing, masks reduced the 15-min mean aerosol concentration at the recipient by 92% at 0.9 and 1.8 m separation. When the simulators were side-by-side, masks reduced the concentration by 81% at 0.9 m and 78% at 1.8 m. During breathing, masks reduced the aerosol concentration by 66% when front-to-front and 76% when side-by-side at 0.9 m. Similar results were seen at 1.8 m. When the simulators were unmasked, changing the orientations from front-to-front to side-by-side reduced the cough aerosol concentration by 59% at 0.9 m and 60% at 1.8 m. When both simulators were masked, changing the orientations did not significantly change the concentration at either distance during coughing or breathing. Increasing the distance between the simulators from 0.9 m to 1.8 m during coughing reduced the aerosol concentration by 25% when no masks were worn but had little effect when both simulators were masked. During breathing, when neither simulator was masked, increasing the separation reduced the concentration by 13%, which approached significance, while the change was not significant when both source and recipient were masked. Our results show that universal masking reduces exposure to respiratory aerosol particles regardless of the orientation and separation distance between the source and recipient.

Economics of Interventions to Increase Active Travel to School: A Community Guide Systematic Review.

CONTEXT: The number of children who bicycle or walk to school has steadily declined in the U.S. and other high-income countries. In response, several countries responded in recent years by funding infrastructure and noninfrastructure programs that improve the safety, convenience, and attractiveness of active travel to school. The objective of this study is to synthesize the economic evidence for the cost and benefit of these programs. EVIDENCE ACQUISITION: Literature from the inception of databases to July 2018 were searched, yielding 9 economic evaluation studies. All analyses were done in September 2018-May 2019. EVIDENCE SYNTHESIS: All the studies reported cost, 6 studies reported cost benefit, and 2 studies reported cost effectiveness. The cost-effectiveness estimates were excluded on the basis of quality assessment. Cost of interventions ranged widely, with higher cost reported for the infrastructure-heavy projects from the U.S. ($91,000-$179,000 per school) and United Kingdom ($227,000-$665,000 per project). Estimates of benefits differed in the inclusion of improved safety for bicyclists and pedestrians, improved health from increased physical activity, and reduced environmental impacts due to less automobile use. The evaluations in the U.S. focused primarily on safety. The overall median benefit‒cost ratio was 4.4:1.0 (IQR=2.2:1-6.0:1, 6 studies). The 2-year benefit-cost ratios for U.S. projects in California and New York City were 1.46:1 and 1.79:1, respectively. CONCLUSIONS: The evidence indicates that interventions that improve infrastructure and enhance the safety and ease of active travel to schools generate societal economic benefits that exceed the societal cost.

Biological effects of inhaled hydraulic fracturing sand dust. IV. Pulmonary effects.

Hydraulic fracturing creates fissures in subterranean rock to increase the flow and retrieval of natural gas. Sand ("proppant") in fracking fluid injected into the well bore maintains fissure patency. Fracking sand dust (FSD) is generated during manipulation of sand to prepare the fracking fluid. Containing respirable crystalline silica, FSD could pose hazards similar to those found in work sites where silica inhalation induces lung disease such as silicosis. This study was performed to evaluate the possible toxic effects following inhalation of a FSD (FSD 8) in the lung and airways. Rats were exposed (6 h/d × 4 d) to 10 or 30 mg/m3 of a FSD collected at a gas well, and measurements were performed 1, 7, 27 and, in one series of experiments, 90 d post-exposure. The following ventilatory and non-ventilatory parameters were measured in vivo and/or in vitro: 1) lung mechanics (respiratory system resistance and elastance, tissue damping, tissue elastance, Newtonian resistance and hysteresivity); 2) airway reactivity to inhaled methacholine (MCh); airway epithelium integrity (isolated, perfused trachea); airway efferent motor nerve activity (electric field stimulation in vitro); airway smooth muscle contractility; ion transport in intact and cultured epithelium; airway effector and sensory nerves; tracheal particle deposition; and neurogenic inflammation/vascular permeability. FSD 8 was without large effect on most parameters, and was not pro-inflammatory, as judged histologically and in cultured epithelial cells, but increased reactivity to inhaled MCh at some post-exposure time points and affected Na+ transport in airway epithelial cells.