N-Acetyl Cysteine Prevents Arterial Thrombosis in a Dose-Dependent Manner In Vitro and in Mice.

BACKGROUND: Platelet-rich thrombi occlude arteries causing fatal infarcts like heart attacks and strokes. Prevention of thrombi by current antiplatelet agents can cause major bleeding. Instead, we propose using N-acetyl cysteine (NAC) to act against the protein VWF (von Willebrand factor), and not platelets, to prevent arterial thrombi from forming. METHODS: NAC was assessed for its ability to prevent arterial thrombosis by measuring platelet accumulation rate and occlusion time using a microfluidic model of arterial thrombosis with human blood. Acute clot formation, clot stability, and tail bleeding were measured in vivo with the murine modified Folts model. The effect of NAC in the murine model after 6 hours was also measured to determine any persistent effects of NAC after it has been cleared from the blood. RESULTS: We demonstrate reduction of thrombi formation following treatment with NAC in vitro and in vivo. Human whole blood treated with 3 or 5 mmol/L NAC showed delayed thrombus formation 2.0× and 3.7× longer than control, respectively (P<0.001). Blood treated with 10 mmol/L NAC did not form an occlusive clot, and no macroscopic platelet aggregation was visible (P<0.001). In vivo, a 400-mg/kg dose of NAC prevented occlusive clots from forming in mice without significantly affecting tail bleeding times. A lower dose of NAC significantly reduced clot stability. Mice given multiple injections showed that NAC has a lasting and cumulative effect on clot stability, even after being cleared from the blood (P<0.001). CONCLUSIONS: Both preclinical models demonstrate that NAC prevents thrombus formation in a dose-dependent manner without significantly affecting bleeding time. This work highlights a new pathway for preventing arterial thrombosis, different from antiplatelet agents, using an amino acid derivative as an antithrombotic therapeutic.

The incidence and impact of enterotomy during laparoscopic and robotic ventral hernia repair: a nationwide readmissions analysis.

INTRODUCTION: Our aim was to define the national incidence of enterotomy (ENT) during minimally invasive ventral hernia repair (MIS-VHR) and evaluate impact on short-term outcomes. METHODS: The 2016-2018 Nationwide Readmissions Database was queried using ICD-10 codes for MIS-VHR and enterotomy. All patients had 3-months follow-up. Patients were stratified by elective status; patients without ENT (No-ENT) were compared against ENT patients. RESULTS: In total, 30,025 patients underwent LVHR and ENT occurred in 388 (1.3%) patients; 19,188 (63.9%) cases were elective including 244 elective-ENT patients. Incidence was similar between elective versus non-elective cohorts (1.27% vs 1.33%; p = 0.674). Compared to laparoscopy, ENT was more common during robotic procedures (1.2% vs 1.7%; p = 0.004). Comparison of elective-No-ENT vs elective-ENT showed that elective-ENT patients had a longer median LOS (2 vs 5 days; p < 0.001), higher mean hospital cost ($51,656 vs $76,466; p < 0.001), increased rates of mortality (0.3% vs 2.9%; p < 0.001), and higher 3-month readmission (10.1% vs 13.9%; p = 0.048). Non-elective cohort comparison demonstrated non-elective-ENT patients had a longer median LOS (4 vs 7 days; p < 0.001), higher mean hospital cost ($58,379 vs $87,850; p < 0.001), increased rates of mortality (0.7% vs 2.1%;p < 0.001), and higher 3-month readmission (13.6% vs 22.2%; p < 0.001). In multivariable analysis (odds ratio, 95% CI), higher odds of enterotomy were associated with robotic-assisted procedures (1.386, 1.095-1.754; p = 0.007) and older age (1.014, 1.004-1.024; p = 0.006). Lower odds of ENT were associated with BMI > 25 kg/m2 (0.784, 0.624-0.984; p = 0.036) and metropolitan teaching vs metropolitan non-teaching (0.784, 0.622-0.987; p = 0.044). ENT patients (n = 388) were more likely to be readmitted with post-operative infection (1.9% vs 4.1%; p = 0.002) or bowel obstruction (1.0% vs 5.2%;p < 0.001) and more likely to undergo reoperation for intestinal adhesions (0.3% vs 1.0%; p = 0.036). CONCLUSION: Inadvertent ENT occurred in 1.3% of MIS-VHRs, had similar rates between elective and urgent cases, but was more common for robotic procedures. ENT patients had a longer LOS, and increased cost and infection, readmission, re-operation and mortality rates.

Multicenter analysis of laparoscopic versus open umbilical hernia repair with mesh: outcomes and quality of life (QoL).

INTRODUCTION: Umbilical hernia repair (UHR) is a common operation with varying surgical approaches. Laparoscopic (LUHR) and open (OUHR) operations are routinely performed, but their impact on quality of life (QoL) is not well described. Our aim was to evaluate perioperative outcomes and QoL of LUHR versus OUHR. METHODS: The prospectively collected International Hernia Mesh Registry was queried for patients undergoing UHR with mesh placement. QoL was measured using the Carolinas Comfort Scale preoperatively and 1, 6, 12, and 24 months postoperatively. Propensity match was performed controlling for hernia defect size (HDS), recurrent hernias, and BMI. RESULTS: 585 patients underwent 178 (30.4%) LUHR and 407 (69.6%) OUHR. LUHR patients had higher BMI, larger HDS, and more recurrent hernias (p < 0.05). Rates of other comorbidities were similar (p > 0.05). Tacks were used more frequently in LUHR (91.6% vs 1.7%, p < 0.001), and suture was used more often in OUHR (97.1% vs 47.8%, p < 0.001). Postoperative outcomes were similar (p > 0.05) except LUHR had higher rates of seroma (13.9% vs 4.3%, p < 0.001). Overall recurrence rates trended to favor OUHR, but not significantly (4.7% vs 8.4%, p = 0.07). The propensity match yielded 138 matched pairs. LUHR had more seromas and OUHR had higher infection rates (p < 0.05). Hernia recurrence was higher following LUHR (9.4% vs 2.9%, p = 0.02). QoL data were available for an average of 457 patients at each time period. QoL was superior in the OUHR group for pain and overall QoL at each time point and activity limitations at 6 and 12 months (p < 0.05). When examining patients who were asymptomatic preoperatively, OUHR had improved one-month overall QoL, but both groups had over 90% of patients report being asymptomatic postoperatively. CONCLUSIONS: OUHR is associated with higher rates of surgical site infections, but significantly lower rates of seroma formation and hernia recurrence compared to LUHR, while having superior QoL in both short- and long-term follow-up. Asymptomatic patients tend to have excellent QoL outcomes.

Thrombogenicity of biomaterials depends on hemodynamic shear rate.

BACKGROUND: While it is well recognized that different biomaterials induce thrombosis at low shear rates, the effect of high shear rates may be quite different. We hypothesize that the amount of thrombus formation on a given material can be greatly influenced by the local shear rate. METHODS: We tested this hypothesis with two different whole blood perfusion loop assays to quantify biomaterial thrombogenicity as a function of shear stress. One assay uses obstructive posts (pins) of material positioned centrally in a tube perfused at high shear rate of >5000/s for 24 h. A second assay uses a parallel plate chamber to perfuse low (<150/s), medium (~500/s), and high shear rates over 96 h. We evaluated the thrombogenicity of seven different biomaterials including stainless steel, acrylic, ceramic, Dacron, polytetrafluoroethylene (PTFE), silicone, and polyvinyl chloride (PVC). RESULTS: For the pin assay, thrombus mass was significantly greater for stainless steel than either zirconia ceramic or acrylic (p < 0.001). Similarly, the parallel plate chamber at high shear showed that steel and PTFE (p < 0.02) occluded the chamber faster than acrylic. In contrast, a low shear parallel plate chamber revealed that stainless steel and PTFE were least thrombogenic, while silicone, Dacron, and other plastics such as acrylic were most thrombogenic. Histology revealed that high shear thrombi had a large proportion of platelets not seen in the low shear fibrin-rich thrombi. CONCLUSION: This differential thrombogenicity based on shear rate conditions may be important in the selection of biomaterials for blood-contacting devices.

Negatively charged nanoparticles of multiple materials inhibit shear-induced platelet accumulation.

Platelet accumulation by VWF under high shear rates at the site of atherosclerotic plaque rupture leads to myocardial infarction and stroke. Current anti-platelet therapies remain ineffective for a large percentage of the population, while presenting significant risks for bleeding. We explore a novel way to inhibit arterial thrombus formation. Theoretically, a negative charge may influence the tertiary structure of VWF to favor the globular configuration by biophysical means without the use of platelet inactivating drugs. We tested this hypothesis experimentally for charged nanoparticles (CNPs) to inhibit thrombus formation in a microfluidic thrombosis assay (MTA). Several different CNPs demonstrated the ability to retard thrombotic occlusion in the MTA. A preliminary study in mice shows that thrombus stability is weaker with CNP administration and bleeding times are not markedly prolonged. The CNPs tested here show promise as a new class of antithrombotic therapies that act by biophysical means rather than biochemical pathways.

Clot Permeability, Agonist Transport, and Platelet Binding Kinetics in Arterial Thrombosis.

The formation of wall-adherent platelet aggregates is a critical process in arterial thrombosis. A growing aggregate experiences frictional drag forces exerted on it by fluid moving over or through the aggregate. The magnitude of these forces is strongly influenced by the permeability of the developing aggregate; the permeability depends on the aggregate's porosity. Aggregation is mediated by formation of ensembles of molecular bonds; each bond involves a plasma protein bridging the gap between specific receptors on the surfaces of two different platelets. The ability of the bonds existing at any time to sustain the drag forces on the aggregate determines whether it remains intact or sheds individual platelets or larger fragments (emboli). We investigate platelet aggregation in coronary-sized arteries using both computational simulations and in vitro experiments. The computational model tracks the formation and breaking of bonds between platelets and treats the thrombus as an evolving porous, viscoelastic material, which moves differently from the background fluid. This relative motion generates drag forces which the fluid and thrombus exert on one another. These forces are computed from a permeability-porosity relation parameterized from experimental measurements. Basing this relation on measurements from occlusive thrombi formed in our flow chamber experiments, along with other physiological parameter values, the model produced stable dense thrombi on a similar timescale to the experiments. When we parameterized the permeability-porosity relation using lower permeabilities reported by others, bond formation was insufficient to balance drag forces on an early thrombus and keep it intact. Under high shear flow, soluble agonist released by platelets was limited to the thrombus and a boundary layer downstream, thus restricting thrombus growth into the vessel lumen. Adding to the model binding and activation of unactivated platelets through von Willebrand-factor-mediated processes allowed greater growth and made agonist-induced activation more effective.

Endograft exclusion of the false lumen restores local hemodynamics in a model of type B aortic dissection.

OBJECTIVE: Endovascular intervention in uncomplicated type B dissection has not been shown conclusively to confer benefit on patients. The hemodynamic effect of primary entry tear coverage is not known. Endovascular stent grafts were deployed in a model of aortic dissection with multiple fenestrations to study these effects. It is hypothesized that endograft deployment will lead to restoration of parabolic true lumen flow as well as elimination of false lumen flow and transluminal jets and vortices locally while maintaining distal false lumen canalization. METHODS: Thoracic stent grafts were placed in silicone models of aortic dissection with a compliant and mobile intimal flap and installed in a flow loop. Pulsatile fluid flow was established with a custom positive displacement pump, and the models were imaged by four-dimensional flow magnetic resonance imaging. Full flow fields were acquired in the models, and velocities were extracted to calculate flow rates, reverse flow indices, and oscillatory shear index, the last two of which are measures of stagnant and disturbed flows. RESULTS: Complete obliteration of the false lumen was achieved in grafted aorta, with normal parabolic flow profiles in the true lumen (maximal velocity, 30.4 ± 8.4 cm/s). A blind false lumen pouch was created distal to this with low-velocity (5.8 ± 2.7 cm/s) and highly reversed (27.9% ± 13.9% reverse flow index) flows. In distal free false lumen segments, flows were comparable to ungrafted conditions with maximal velocities on the order of 7.0 ± 2.1 cm/s. Visualization studies revealed forward flow in these regions with left-handed vortices from true to false lumen. Shear calculations in free false lumen regions demonstrated reduced oscillatory shear index. CONCLUSIONS: Per the initial hypothesis, endovascular grafting improved true lumen hemodynamics in the grafted region. Just distally, a prothrombotic flow regimen was noted in the false lumen, yet free false lumen distal to this remained canalized. Clinically, this suggests a need for advancing endovascular intervention beyond sole entry tear coverage to prevent further false lumen canalization through uncovered fenestrations.

Who Create Jobs? Venture Capital, Research Grants, and Regional Employment in the U.S.

We build on the exploratory and exploitative learning literature that suggests that venture capital and governmental research grants may impact regional employment in a different manner. Using a regional employment dataset in the U.S. medical device sector, our analysis reveals that research grants contribute to create a greater level of regional employment compared with venture capital funding. Furthermore, the positive effects of both funding sources are more salient when intellectual capital is abundant in the region. More specifically, the interaction effect of research grants and intellectual capital is gradually increased in the long term and eventually becomes greater than that of venture capital and intellectual capital, which is relatively constant. These findings highlight the heterogeneous motivations and consequences of two funding sources that should be considered in the future resource allocation policy accordingly.

Thrombus Formation at High Shear Rates.

The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. A high-shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Thrombosis at high shear rates depends primarily on the long protein von Willebrand factor (vWF) and platelets, with hemodynamics playing an important role in each stage of thrombus formation, including vWF binding, platelet adhesion, platelet activation, and rapid thrombus growth. The prediction of high-shear thrombosis is a major area of biofluid mechanics in which point-of-care testing and computational modeling are promising future directions for clinically relevant research. Further research in this area will enable identification of patients at high risk for arterial thrombosis, improve prevention and treatment based on shear-dependent biological mechanisms, and improve blood-contacting device design to reduce thrombosis risk.

Flow and wall shear stress characterization after endovascular aneurysm repair and endovascular aneurysm sealing in an infrarenal aneurysm model.

BACKGROUND: Endovascular aneurysm repair (EVAR) with a modular endograft has become the preferred treatment for abdominal aortic aneurysms. A novel concept is endovascular aneurysm sealing (EVAS), consisting of dual endoframes surrounded by polymer-filled endobags. This dual-lumen configuration is different from a bifurcation with a tapered trajectory of the flow lumen into the two limbs and may induce unfavorable flow conditions. These include low and oscillatory wall shear stress (WSS), linked to atherosclerosis, and high shear rates that may result in thrombosis. An in vitro study was performed to assess the impact of EVAR and EVAS on flow patterns and WSS. METHODS: Four abdominal aortic aneurysm phantoms were constructed, including three stented models, to study the influence of the flow divider on flow (Endurant [Medtronic, Minneapolis, Minn], AFX [Endologix, Irvine, Calif], and Nellix [Endologix]). Experimental models were tested under physiologic resting conditions, and flow was visualized with laser particle imaging velocimetry, quantified by shear rate, WSS, and oscillatory shear index (OSI) in the suprarenal aorta, renal artery (RA), and common iliac artery. RESULTS: WSS and OSI were comparable for all models in the suprarenal aorta. The RA flow profile in the EVAR models was comparable to the control, but a region of lower WSS was observed on the caudal wall compared with the control. The EVAS model showed a stronger jet flow with a higher shear rate in some regions compared with the other models. Small regions of low WSS and high OSI were found near the distal end of all stents in the common iliac artery compared with the control. Maximum shear rates in each region of interest were well below the pathologic threshold for acute thrombosis. CONCLUSIONS: The different stent designs do not influence suprarenal flow. Lower WSS is observed in the caudal wall of the RA after EVAR and a higher shear rate after EVAS. All stented models have a small region of low WSS and high OSI near the distal outflow of the stents.

Hemodynamic studies of platelet thrombosis using microfluidics.

Platelets contribute to thrombus formation in a variety of ways. Platelet adhesion, activation, and thrombus growth depend greatly on the type of hemodynamic environment surrounding an inciting event. Microfluidic systems may be used to explore these relationships. In this review, we describe some important considerations required in the design of a microfluidic system and identify some limitations that may require use of a macroscale system.

In vivo evaluation of the bone integration of coated poly(vinyl-alcohol) hydrogel fiber implants.

Recently, it has been shown that constructs of poly(vinyl alcohol) (PVA) hydrogel fibers reproduce closely the tensile behavior of ligaments. However, the biological response to these systems has not been explored yet. Here, we report the first in vivo evaluation of these implants and focus on the integration in bone, using a rabbit model of bone tunnel healing. Implants consisted in bundles of PVA hydrogel fibers embedded in a PVA hydrogel matrix. Half of the samples were coated with a composite coating of hydroxyapatite (HA) particles embedded in PVA hydrogel. The biological integration was evaluated at 6 weeks using histology and micro-CT imaging. For all implants, a good biological tolerance and growth of new bone tissue are reported. All the implants were surrounded by a fibrous layer comparable to what was previously observed for poly(ethylene terephthalate) (PET) fibers currently used in humans for ligament reconstruction. An image analysis method is proposed to quantify the thickness of this fibrous capsule. Implants coated with HA were not significantly osteoconductive, which can be attributed to the slow dissolution of the selected hydroxyapatite. Overall, these results confirm the relevance of PVA hydrogel fibers for ligament reconstruction and adjustments are proposed to enhance its osseointegration.

Role of high shear rate in thrombosis.

Acute arterial occlusions occur in high shear rate hemodynamic conditions. Arterial thrombi are platelet-rich when examined histologically compared with red blood cells in venous thrombi. Prior studies of platelet biology were not capable of accounting for the rapid kinetics and bond strengths necessary to produce occlusive thrombus under these conditions where the stasis condition of the Virchow triad is so noticeably absent. Recent experiments elucidate the unique pathway and kinetics of platelet aggregation that produce arterial occlusion. Large thrombi form from local release and conformational changes in von Willebrand factor under very high shear rates. The effect of high shear hemodynamics on thrombus growth has profound implications for the understanding of all acute thrombotic cardiovascular events as well as for vascular reconstructive techniques and vascular device design, testing, and clinical performance.

Development and testing of a silicone in vitro model of descending aortic dissection.

BACKGROUND: Stanford type B dissection of the descending aorta is a potentially fatal condition that is poorly understood. Limited scientific understanding of the role of current interventional techniques, as well as heterogeneity in the condition, contributes to lack of consensus as to the most effective treatment strategy. This study introduces an anatomically accurate model for investigating aortic dissection in a laboratory setting. MATERIALS AND METHODS: A silicone model was fabricated and filled with fluid to mimic human blood. Flow was established, and the model was scanned using a four-dimensional flow magnetic resonance imaging protocol. On analysis, luminal flow rates were quantified by multiplying local velocity by included area. RESULTS: The upstream total flow was compared with the sum of the flow in the true and false lumens. The two values were within the margin of error. Furthermore, flow rates matched with the relative areas of each compartment. CONCLUSIONS: These results validate our model as a novel and unique system that mimics a type B aortic dissection and will allow for more sophisticated analysis of dissection physiology in future studies.

Geometric design of microfluidic chambers: platelet adhesion versus accumulation.

Arterial, platelet-rich thrombosis depends on shear rates and integrin binding to either a collagen surface or to the growing thrombus, which are mechanistically different. In general, small microfluidic test sections may favor platelet-surface adhesion without testing for the primary mode of intra-arterial thrombosis, i.e. platelet-platelet bonding and accumulation. In the present report, the ratio of platelet-platelet to platelet-surface interactions, R, and the percentage of platelet-platelet interactions, P, are estimated using an analytical approach for circular and rectangular test sections. Results show that the test section geometry strongly affects both R and P, with test section height in low-aspect ratio channels or diameter greater than 90 µm dominated by platelet-platelet interactions (R >10). Increasing rectangular test section aspect ratio decreases the required height. R increases linearly while P approaches 100 % asymptotically with increasing channel dimension. Analysis of platelet shape shows that the assumption of spherical platelets has a small effect on R compared to discoid platelets adhering flat against test section wall. However, an increase in average platelet volume resulted in a large decrease in R. Nonetheless, Monte Carlo simulations of a typical distribution of human platelet sizes show intrasubject variation in platelet size has only a 10 % net effect on R. Finally, experiments of thrombus formation show that platelet-surface lag times and platelet-platelet accumulation are similar for rectangular microfluidic test sections and round test sections when R >10. The findings show that the size of a microfluidic test section should be carefully considered in studies of cell-cell accumulation versus cell-surface adhesion.

Material strengths of shear-induced platelet aggregation clots and coagulation clots.

Arterial occlusion by thrombosis is the immediate cause of some strokes, heart attacks, and peripheral artery disease. Most prior studies assume that coagulation creates the thrombus. However, a contradiction arises as whole blood (WB) clots from coagulation are too weak to stop arterial blood pressures (> 150 mmHg). We measure the material mechanical properties of elasticity and ultimate strength for Shear-Induced Platelet Aggregation (SIPA) type clots, that form under stenotic arterial hemodynamics in comparison with coagulation clots. The ultimate strength of SIPA clots averaged 4.6 ± 1.3 kPa, while WB coagulation clots had a strength of 0.63 ± 0.3 kPa (p < 0.05). The elastic modulus of SIPA clots was 3.8 ± 1.5 kPa at 1 Hz and 0.5 mm displacement, or 2.8 times higher than WB coagulation clots (1.3 ± 1.2 kPa, p < 0.0001). This study shows that the SIPA thrombi, formed quickly under high shear hemodynamics, is seven-fold stronger and three-fold stiffer compared to WB coagulation clots. A force balance calculation shows a SIPA clot has the strength to resist arterial pressure with a short length of less than 2 mm, consistent with coronary pathology.

Detection of pathogenic bacteria and biomarkers in lung specimens from cystic fibrosis patients.

Diagnosing lung infections is often challenging because of the lack of a high-quality specimen from the diseased lung. Since persons with cystic fibrosis are subject to chronic lung infection, there is frequently a need for a lung specimen. In this small, proof of principle study, we determined that PneumoniaCheckTM, a non-invasive device that captures coughed droplets from the lung on a filter, might help meet this need. We obtained 10 PneumoniaCheckTMcoughed specimens and 2 sputum specimens from adult CF patients hospitalized with an exacerbation of their illness. We detected amylase (upper respiratory tract) with an enzymatic assay, surfactant A (lower respiratory tract) with an immunoassay, pathogenic bacteria by PCR, and markers of inflammation by a Luminex multiplex immunoassay. The amylase and surfactant A levels suggested that 9/10 coughed specimens were from lower respiratory tract with minimal upper respiratory contamination. The PCR assays detected pathogenic bacteria in 7 of 9 specimens and multiplex Luminex assay detected a variety of cytokines or chemokines. These data indicate that the PneumoniaCheckTMcoughed specimens can capture good quality lower respiratory tract specimens that have the potential to help in diagnosis, management and understanding of CF exacerbations and other lung disease.

Novel tubing connectors reduce ECMO circuit thrombosis.

BACKGROUND: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions. METHODS: A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi. To compare clotting between the novel connectors and the traditional connectors, both in vitro loops and an in vivo caprine model of long-term (48 h) ECMO were used to generate tubing-connector junction clots. RESULTS: In vitro, the traditional connectors uniformly (9/9) formed large thrombi, while novel connectors formed a small thrombus in only one of nine (p < 0.0001). In the long-term goat ECMO circuits, the traditional connectors exhibited more thrombi (p < 0.04), and these thrombi were more likely to protrude into the lumen of the tubing (p < 0.001). CONCLUSION: Both in vitro and in vivo validation experiments successfully recreated circuit thrombosis and demonstrate that the adoption of novel connectors can reduce the burden of circuit thrombosis.

A novel aerosol collection method shows the cough aeromicrobiome of people with tuberculosis is phylogenetically distinct from respiratory tract specimens.

Background: Tuberculosis (TB), a major cause of disease and antimicrobial resistance, is spread via aerosols. Aerosols have diagnostic potential and airborne-microbes other than Mycobacterium tuberculosis complex (MTBC) may influence transmission. We evaluated whether PneumoniaCheck (PMC), a commercial aerosol collection device, captures MTBC and the aeromicrobiome of people with TB. Methods: PMC was done in sputum culture-positive people (≥30 forced coughs each, n=16) pre-treatment and PMC air reservoir (bag, corresponding to upper airways) and filter (lower airways) washes underwent Xpert MTB/RIF Ultra (Ultra) and 16S rRNA gene sequencing (sequencing also done on sputum). In a subset (n=6), PMC microbiota (bag, filter) was compared to oral washes and bronchoalveolar lavage fluid (BALF). Findings: 54% (7/13) bags and 46% (6/14) filters were Ultra-positive. Sequencing read counts and microbial diversity did not differ across bags, filters, and sputum. However, microbial composition in bags (Sphingobium-, Corynebacterium-, Novosphingobium-enriched) and filters (Mycobacterium-, Sphingobium-, Corynebacterium-enriched) each differed vs. sputum. Furthermore, sequencing only detected Mycobacterium in bags and filters but not sputum. In the subset, bag and filter microbial diversity did not differ vs. oral washes or BALF but microbial composition differed. Bags vs. BALF were Sphingobium-enriched and Mycobacterium-, Streptococcus-, and Anaerosinus-depleted (Anaerosinus also depleted in filters vs. BALF). Compared to BALF, none of the aerosol-enriched taxa were enriched in oral washes or sputum. Interpretation: PMC captures aerosols with Ultra-detectable MTBC and MTBC is more detectable in aerosols than sputum by sequencing. The aeromicrobiome is distinct from sputum, oral washes and BALF and contains differentially-enriched lower respiratory tract microbes.