GM-CSF Promotes Immune Response and Survival in a Mouse Model of COVID-19.

COVID-19 results in increased expression of inflammatory cytokines, but inflammation-targeting clinical trials have yielded poor to mixed results. Our studies of other disorders with an inflammatory component, including Alzheimer's disease, chemobrain, Down syndrome, normal aging, and West Nile Virus infection, showed that treatment with the 'pro-inflammatory' cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) in humans or mouse models alleviated clinical, behavioral, and pathological features. We proposed that human recombinant GM-CSF (sargramostim) be repurposed to promote both the innate and adaptive immune responses in COVID-19 to reduce viral load and mortality1. Here, we report the results of a placebo-controlled study of GM-CSF in human ACE2 transgenic mice inoculated intranasally with SARS-CoV2 virus, a model of COVID-19. Infection resulted in high viral titers in lungs and brains and over 85% mortality. GM-CSF treatment beginning one day after infection increased anti-viral antibody titers, lowered mean lung viral titers proportionately (p=0.0020) and increased the odds of long-term survival by up to 5.8-fold (p=0.0358), compared to placebo. These findings suggest that, as an activator of both the innate and adaptive immune systems, GM-CSF/sargramostim may be an effective COVID-19 therapy with the potential to protect from re-infection more effectively than treatment with antiviral drugs or monoclonal antibodies.

Vitamin D Status and Clinical Outcomes in Acute Respiratory Distress Syndrome: A Secondary Analysis From the Assessment of Low Tidal Volume and Elevated End-Expiratory Volume to Obviate Lung Injury (ALVEOLI) Trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a highly morbid condition that has limited therapeutic options. Optimal vitamin D status has been linked to immunological effects that may benefit critically ill patients. Therefore, we investigated whether admission 25-hydroxyvitamin D levels (25OHD) are associated with clinical outcomes in ARDS patients. METHODS: We performed a secondary analysis of data from a randomized, controlled trial comparing oxygenation strategies in 549 patients with ARDS (NCT00000579). Baseline 25OHD was measured in stored plasma samples. We investigated the relationship between vitamin D status and ventilator-free days (VFD) as well as 90-day survival, using linear regression and Cox proportional hazard models, respectively. Analyses were adjusted for age, race, and Acute Physiology and Chronic Health Evaluation III score. RESULTS: Baseline 25OHD was measured in 476 patients. 90% of these individuals had 25OHD <20 ng/ml and 40% had 25OHD <10 ng/ml. Patients with 25OHD <20 ng/ml were likely to be ventilated for 3 days longer than patients with levels ≥20 ng/ml (ß 3.41; 95%CI 0.42-6.39: P = 0.02). Patients with 25OHD <10 ng/ml were likely to be ventilated for 9 days longer (ß 9.27; 95%CI 7.24-11.02: P < 0.001) and to have a 34% higher risk of 90-day mortality (HR 1.34; 95% CI 1.06-1.71: P = 0.02) compared to patients with levels >10 ng/ml. CONCLUSIONS: In patients with ARDS, vitamin D status is associated with duration of mechanical ventilation and 90-day mortality. Randomized, controlled trials are warranted to determine whether vitamin D supplementation improves clinical outcomes in ARDS patients.

Correlation of serum protein biomarkers with disease activity in psoriatic arthritis.

Objective: To assess the correlation of serum protein biomarkers with disease activity across different domains of psoriatic arthritis (PsA).Material and methods: A cross-sectional cohort of 45 adult patients with PsA fulfilling the classification for psoriatic arthritis (CASPAR) criteria was recruited from University of California San Diego (UCSD) Arthritis Clinics. Clinical data and serum samples were collected and serum was analyzed for protein biomarkers hypothesized to be relevant to disease activity in PsA. Correlations were evaluated for clinical disease activity measures across disease domains.Results: Biomarkers with the highest correlation to the composite indices and disease domains were SAA, IL-6, YKL-40, and ICAM-1. In addition, several biomarkers were moderately correlated with individual composite indices and/or disease domains. Low or no correlation was observed with some biomarkers, e.g. MMP-3, MMP-1, EGF, VEGF, and IL-6R. In contrast, the correlation of all biomarkers with certain disease domains was low; specifically, pain, percent body surface area of psoriasis, and patient global assessment. The multi-biomarker disease activity score (MBDA) developed for rheumatoid arthritis (RA) showed high correlations with most composite indices and some disease domains in PsA.Conclusions: These data suggest biomarker analysis can reflect disease activity across disease domains in PsA. Certain domains would likely benefit from the evaluation of additional biomarkers.

Persistence of low disease activity after tumour necrosis factor inhibitor (TNFi) discontinuation in patients with psoriatic arthritis.

OBJECTIVE: To determine the duration of clinical benefit among patients with psoriatic arthritis (PsA) discontinuing tumour necrosis factor inhibitor (TNFi) therapy while in low disease activity (LDA), and to identify patient characteristics associated with prolonged clinical benefit. METHODS: We performed an observational cohort study assessing patients with PsA from the Consortium of Rheumatology Researchers of North America (CORRONA) registry who had discontinued TNFi after achieving LDA, defined as clinical disease activity index (CDAI) score ≤10 and physician's global assessment (PGA) of skin psoriasis ≤20/100. Kaplan-Meier method was used to estimate the duration of clinical benefit. RESULTS: Of the 5945 patients with PsA in CORRONA, 302 patients had discontinued TNFi (n=325) while in LDA and had follow-up data available. At time of discontinuation, mean PsA duration was 9.8 years, mean CDAI was 3.9, and mean duration of TNFi use was 1.5 years; 52.6% of patients had discontinued their first TNFi. Median time to loss of benefit was 29.2 months. 179 (55.1%) patients had persistent benefit at their previous clinic visit. An increased risk of losing clinical benefit was seen among patients with higher disease activity at discontinuation (CDAI≥3.2 vs <3.2; HR 1.43 (p=0.32)) and among smokers (HR 1.78 (p=0.027)). CONCLUSIONS: Patients with PsA who achieve LDA may maintain clinical benefit after discontinuation of TNFi therapy.

Prevalence and risk factors of chorioamnionitis in Dhaka, Bangladesh.

OBJECTIVE: To estimate the association between chorioamnionitis, maternal risk factors and birth outcomes. STUDY DESIGN: A cross-sectional study of 600 pregnant women was conducted at a maternity center in Dhaka from January to October 2011. Outcomes included histologic, microbiologic and clinical chorioamnionitis. Log-binomial models assessed the association between risk factors and histologic chorioamnionitis (HC). RESULTS: Of the 552 women with placental specimens, 70 (12.7%) were classified with HC: 46 (65.7%) with and 24 (34.3%) without fetal involvement. HC was associated with non-physician care (relative risk [RR] 2.04, 95% confidence interval [CI] 1.04 to 4.00), home slab or hanging latrine (RR 1.69, 95% CI 1.10 to 2.62), and lack of tetanus toxoid (RR 1.80, 95% CI 1.03 to 3.14). Women with fever (RR 2.30, 95% CI 1.18 to 4.50) or discolored amniotic fluid (RR 1.74, 95% CI 1.08 to 2.81) had a higher risk of HC. Microbiologic and clinical chorioamnionitis were unreliable HC measures. CONCLUSION: Prevalence of HC is high; many cases are not captured by clinical diagnosis or microbiologic cultures.

Safe Tummy Tuck: Anatomy and Strategy to Avoid Injury to the Lateral Femoral Cutaneous Nerve During Abdominoplasty.

BACKGROUND: Abdominoplasty is one of the most common aesthetic procedures performed in the United States. While poor contour and unsatisfactory cosmetic result have been recognized, neuropathic pain from lateral femoral cutaneous nerve injury has been poorly described. We aim to improve outcomes by using an anatomical study to develop a strategy to avoid injury to the lateral femoral cutaneous nerve in abdominoplasty. METHODS: Twenty-three fresh cadaver abdomens were dissected to evaluate the course of the lateral femoral cutaneous nerve, using 2.5× loupe magnification. Measurements were taken from the nerve to the anterior superior iliac spine and from the pubic symphysis to the lateral femoral cutaneous nerve. Recordings of the relationship of the nerve to the inguinal ligament and depth at scarpa's fascia were also made. Statistical analysis was performed to find average distances with a standard deviation. RESULTS: On average, the distance from the lateral femoral cutaneous nerve to the anterior superior iliac spine was 3.62 (SD = 1.32) cm and 13.58 (SD = 2.41) cm from the pubic symphysis in line with the inguinal ligament. The lateral femoral cutaneous nerve was found at the inguinal ligament 80% of the time and 20% of the time superior to the ligament and always deep to scarpa's fascia. CONCLUSION: Abdominoplasty carries a high patient and surgeon satisfaction rate. The plastic surgeon is continuously challenged to identify ways to improve outcomes, efficiency, and morbidity. Minimal and careful dissection in the area around 4 cm of the anterior superior iliac spine in addition to preserving scarpa's fascia near the inguinal ligament may serve as key strategies to avoiding lateral femoral cutaneous nerve injury.

Combined radiocarbon and CO2 flux measurements used to determine in situ chlorinated solvent mineralization rate.

A series of combined measurements was made at the Naval Air Station North Island (NASNI) Installation Restoration Site 5, Unit 2 during July and August 2013. Combined measurements included CO2 respiration rate, CO2 radiocarbon content to estimate chlorinated hydrocarbon (CH) mineralization and a zone of influence (ZOI) model. CO2 was collected continuously over 2 two-week periods by recirculating monitoring well headspace gas through NaOH traps. A series of 12 wells in the main CH plume zone and a background well with no known historical contamination were sampled. The background well CO2 was used to determine radiocarbon content derived from respired natural organic matter. A two end-member mixing model was then used to determine the amount of CH-derived carbon present in the CO2 collected from plume region wells. The ZOI model provided an estimate for the soil volume sampled at each well. CH mineralization rates were highest upgradient and at the plume fringe for areas of high historical contamination and ranged from 0.02 to 5.6 mg CH carbon per day. Using the ZOI model volume estimates, CH-carbon removal ranged from 0.2 to 32 mg CH-carbon m(-3) per day. Because the rate estimates were based on a limited sampling (temporally), they were not further extrapolated to long-term contaminant degradation estimates. However, if the site manager or regulators required them, estimates - subject to long-term variability uncertainties - could be made using volume and rate data determined over short timescales. A more comprehensive seasonal sampling is needed to constrain long-term remediation models for the entire impacted area and identify environmental conditions related to more rapid turnover times amongst the wells.

Evidence for divisome localization mechanisms independent of the Min system and SlmA in Escherichia coli.

Cell division in Escherichia coli starts with assembly of FtsZ protofilaments into a ring-like structure, the Z-ring. Positioning of the Z-ring at midcell is thought to be coordinated by two regulatory systems, nucleoid occlusion and the Min system. In E. coli, nucleoid occlusion is mediated by the SlmA proteins. Here, we address the question of whether there are additional positioning systems that are capable of localizing the E. coli divisome with respect to the cell center. Using quantitative fluorescence imaging we show that slow growing cells lacking functional Min and SlmA nucleoid occlusion systems continue to divide preferentially at midcell. We find that the initial Z-ring assembly occurs over the center of the nucleoid instead of nucleoid-free regions under these conditions. We determine that Z-ring formation begins shortly after the arrival of the Ter macrodomain at the nucleoid center. Removal of either the MatP, ZapB, or ZapA proteins significantly affects the accuracy and precision of Z-ring positioning relative to the nucleoid center in these cells in accordance with the idea that these proteins link the Ter macrodomain and the Z-ring. Interestingly, even in the absence of Min, SlmA, and the putative Ter macrodomain - Z-ring link, there remains a weak midcell positioning bias for the Z-ring. Our work demonstrates that additional Z-ring localization systems are present in E. coli than are known currently. In particular, we identify that the Ter macrodomain acts as a landmark for the Z-ring in the presence of MatP, ZapB and ZapA proteins.

An exploratory investigation of real-world reasoning in paranoia.

OBJECTIVES: Paranoid thinking has been linked to greater availability in memory of past threats to the self. However, remembered experiences may not always closely resemble events that trigger paranoia, so novel explanations must be elaborated for the likelihood of threat to be determined. We investigated the ability of paranoid individuals to construct explanations for everyday situations and whether these modulate their emotional impact. METHODS: Twenty-one participants experiencing paranoia and 21 healthy controls completed a mental simulation task that yields a measure of the coherence of reasoning in everyday situations. RESULTS: When responses featured positive content, clinical participants produced less coherent narratives in response to paranoid themed scenarios than healthy controls. There was no significant difference between the groups when responses featured negative content. CONCLUSIONS: The current study suggests that difficulty in scenario construction may exacerbate paranoia by reducing access to non-threatening explanations for everyday events, and this consequently increases distress.

Eruptive and functional changes in periodontal ligament fibroblast orientation in CD44 wild-type vs. knockout mice.

BACKGROUND AND OBJECTIVE: Periodontal ligament (PDL) fibroblasts establish principal fibers of the ligament during tooth eruption, and maintain these fibers during occlusion. PDL development and occlusal adaptation includes changes in the orientation of PDL fibroblasts; however, the mechanism for these changes in orientation is unclear. The objective of this study was to compare PDL fibroblast orientation in different stages corresponding with first molar eruption and occlusion in CD44 wild-type (WT) and knockout (KO) mice. MATERIAL AND METHODS: CD44 WT and KO mice were raised to six postnatal stages corresponding with first molar (M1 ) eruption (postnatal day 8, 11, 14 and 18) and occlusion (postnatal day 26 and 41). Coronal sections of the first mandibular molar (M1 ) were prepared and the orientation of fibroblasts in the cervical root region was measured. Angle measurements were compared across developmental stages and between strains using Watson-Williams F-test (oriana software) and ANCOVA. RESULTS: PDL fibroblast orientation increased significantly in CD44 WT (9-87°) and KO mice (14-93°; p ≤ 0.05) between intraosseous eruption (day 11), mucosal penetration (day 14) and preocclusal eruption (day 18); however, the PDL fibroblast orientation did not change significantly with the onset of occlusion (day 26) or continued function (day 41). Within each strain, the variance in fibroblast orientation during preocclusal eruption (day 18) was significantly higher than the variance of all other time points (p < 0.0005). CD44 WT and KO mice showed a similar pattern of PDL development and eruption with a significant difference in CD44 WT vs. KO fibroblast orientations only during early function (day 26, 92° vs 116°; p = 0.05). CONCLUSIONS: The development of PDL fibroblast orientation is highly similar between CD44 WT and KO mice. Between early (day 11) and late (day 18) eruptive stages PDL fibroblast orientation increases, corresponding with the upward movement of M1 . The PDL fibroblast orientation established in preocclusal eruption (day 18) is maintained during early (day 26) and late (day 41) stages of occlusal function, suggesting that PDL cells adapt to mechanical loads in the oral cavity before M1 occlusion.

Extracorporeal membrane oxygenation to support whole-lung lavage in pulmonary alveolar proteinosis: salvage of the drowned lungs.

Pulmonary alveolar proteinosis is a rare lung disease characterized by accumulation of lipoproteinaceous material within the alveoli. Therapeutic whole-lung lavage (WLL) under general anesthesia is the standard treatment in patients with progressive symptomatic disease. Severe hypoxemic respiratory failure is uncommon, yet when present poses a technical challenge to performing WLL without further compromising respiratory status. Rarely, hyperbaric chamber or extracorporeal membrane oxygenation (ECMO) has been utilized to perform WLL to manage severe hypoxemia, with venovenous ECMO being used more often. We present a case of hypoxemic and hypercarbic respiratory failure from pulmonary alveolar proteinosis successfully managed by placing the patient on venoarterial ECMO to facilitate the performance of bilateral WLL.

Plasma effects on harmonic spectra generated from moderately relativistic laser-plasma interactions.

When intense p-polarized laser light is incident on a plasma with an electron density many times the critical density, the flux of fast electrons created by Brunel absorption excites plasma oscillations. These oscillations may in turn affect the spectrum of high harmonics by modulating the spectrum at the plasma frequency, ω(p), and by coupling to the radiation field through the steep density gradient at the plasma-vacuum interface, so generating plasma line emission (PLE) at ω(p) and harmonics of ω(p). Both aspects depend sensitively on a range of plasma and laser pulse parameters, including the initial electron density, the density profile at the plasma-vacuum interface, and the intensity, pulse shape, and pulse length of the incident laser light. These various dependences have been characterised for moderately relativistic laser-plasma interactions by means of a series of particle-in-cell (PIC) simulations.

A Public Health Grid (PHGrid): Architecture and value proposition for 21st century public health.

PURPOSE: This manuscript describes the value of and proposal for a high-level architectural framework for a Public Health Grid (PHGrid), which the authors feel has the capability to afford the public health community a robust technology infrastructure for secure and timely data, information, and knowledge exchange, not only within the public health domain, but between public health and the overall health care system. METHODS: The CDC facilitated multiple Proof-of-Concept (PoC) projects, leveraging an open-source-based software development methodology, to test four hypotheses with regard to this high-level framework. The outcomes of the four PoCs in combination with the use of the Federal Enterprise Architecture Framework (FEAF) and the newly emerging Federal Segment Architecture Methodology (FSAM) was used to develop and refine a high-level architectural framework for a Public Health Grid infrastructure. RESULTS: The authors were successful in documenting a robust high-level architectural framework for a PHGrid. The documentation generated provided a level of granularity needed to validate the proposal, and included examples of both information standards and services to be implemented. Both the results of the PoCs as well as feedback from selected public health partners were used to develop the granular documentation. CONCLUSIONS: A robust high-level cohesive architectural framework for a Public Health Grid (PHGrid) has been successfully articulated, with its feasibility demonstrated via multiple PoCs. In order to successfully implement this framework for a Public Health Grid, the authors recommend moving forward with a three-pronged approach focusing on interoperability and standards, streamlining the PHGrid infrastructure, and developing robust and high-impact public health services.

Gross abnormalities of the umbilical cord: related placental histology and clinical significance.

OBJECTIVE: To evaluate umbilical cord abnormalities predisposing to mechanical cord compression and determine their relationship to adverse clinical outcomes and stasis-associated histologic changes in the placenta. METHODS: Placental slides of 224 singleton pregnancies with gross cord abnormality (true knots, long cords, nuchal/body cords, abnormal cord insertion, hypercoiled cords, narrow cords with diminished Wharton's jelly), delivered on or after 28 weeks gestational age, and 317 gestational age-matched controls, were reviewed and specifically evaluated for the following histologic changes: (1) fetal vascular ectasia, (2) fetal vascular thrombosis, (3) and fetal thrombotic vasculopathy/avascular villi. These changes were analyzed in relation to both clinical information and findings at gross pathologic examination. RESULTS: Gross cord abnormalities were associated with stillbirth, intrauterine growth restriction, non-reassuring fetal tracing, meconium-stained amniotic fluid, and increased rate of emergency Cesarean section. At microscopic evaluation, cases with gross cord abnormalities showed a statistically significant association with both ectasia and thrombosis in the fetal vasculature, as well as changes of fetal thrombotic vasculopathy in the terminal villi. When considering individual gross cord abnormalities, long cord and nuchal cord had the highest rates of thrombosis-related histopathology. Finally, cases with both abnormal cords and histologic thrombosis had significantly higher rates of adverse outcomes, including IUGR and stillbirth. CONCLUSION: Gross cord abnormalities predispose the fetus to stasis-induced vascular ectasia and thrombosis, thus leading to vascular obstruction and adverse neonatal outcome, including IUGR and stillbirth. We recommend a thorough histopathologic evaluation of all placentas with gross cord abnormalities predisposing to cord compression.

Anomalies in universal intensity scaling in ultrarelativistic laser-plasma interactions.

Laser light incident on targets at intensities such that the electron dynamics is ultrarelativistic gives rise to a harmonic power spectrum extending to high orders and characterized by a relatively slow decay with the harmonic number m that follows a power law dependence, m(-p). Relativistic similarity theory predicts a universal value for p=8/3 up to some cutoff m=m*. The results presented in this Letter suggest that under conditions in which plasma effects contribute to the emission spectrum, the extent of this contribution may invalidate the concept of universal decay. We report a decay with the harmonic number in the ultrarelativistic range characterized by an index 5/3 < or approximately p < or approximately 7/3, significantly weaker than that predicted by the similarity model.

Reduction of VSC and salivary bacteria by a multibenefit mouthrinse.

To evaluate the effectiveness of a multibenefit mouthrinse containing 0.05% cetylpyridinium chloride (CPC) and 0.025% sodium fluoride in reducing volatile sulfur compound (VSC) levels and total cultivable salivary bacteria, at both 4 h and overnight. In vitro analysis of efficacy was performed using saliva-coated hydroxyapatite disc substrates first treated with the mouthrinse, then exposed to whole human saliva, followed by overnight incubation in air-tight vials. Headspace VSC was quantified by gas chromatography (GC). A clinical evaluation was conducted with 14 subjects using a crossover design. After a seven-day washout period, baseline clinical measurement of VSC was performed by GC analysis of mouth air sampled in the morning prior to eating, drinking or performing any oral hygiene. A 10 mL saline rinse was used to sample and enumerate cultivable salivary bacterial levels via serial dilution and plating. Subjects were instructed to use the treatment rinse twice daily in combination with a controlled brushing regimen. After one week the subjects returned in the morning prior to eating, drinking or performing oral hygiene to provide samples of overnight mouth air and salivary bacteria. The subjects were then immediately rinsed with the test product, and provided additional mouth air and saliva rinse samples 4 h later. A multibenefit rinse containing 0.05% CPC and 0.025% sodium fluoride was found to reduce VSC in vitro by 52%. The rinse also demonstrated a significant clinical reduction in breath VSC (p < 0.05) of 55.8% at 4 h and 23.4% overnight relative to baseline VSC levels. At both time points, the multibenefit rinse was more effective than the control; this difference was statistically significant at the overnight time point (p < 0.05). Total cultivable salivary bacteria levels were also reduced significantly (p < 0.05) at 4 h and overnight by this mouthrinse compared to baseline levels and the control. A multibenefit mouthrinse was shown to reduce in vitro VSC levels via headspace analysis and clinically at the 4 h and overnight time points. A significant reduction in total cultivable salivary bacteria was also observed at all time points, supporting the VSC data.

Plasma modulation of harmonic emission spectra from laser-plasma interactions.

We report results from particle-in-cell simulations of the interaction of intense laser light with overdense plasma designed to examine the effects of plasma waves generated by pulses of fast electrons on high-order harmonic emission from the plasma. We show that the emission spectrum is modulated at the plasma frequency and identify combinations of parameters and circumstances favorable for modulation. In particular, the observed modulation is shown to depend not only on the chosen plasma electron density and intensity of the incident light but on the density profile and pulse shape.

Findings from aCGH in patients with congenital diaphragmatic hernia (CDH): a possible locus for Fryns syndrome.

Congenital diaphragmatic hernia (CDH) is a common and often devastating birth defect that can occur in isolation or as part of a malformation complex. Considerable progress is being made in the identification of genetic causes of CDH. We applied array-based comparative genomic hybridization (aCGH) of approximately 1Mb resolution to 29 CDH patients with prior normal karyotypes who had been recruited into our multi-site study. One patient, clinically diagnosed with Fryns syndrome, demonstrated a de novo 5Mb deletion at chromosome region 1q41-q42.12 that was confirmed by FISH. Given prior reports of CDH in association with cytogenetic abnormalities in this region, we propose that this represents a locus for Fryns syndrome, a Fryns syndrome phenocopy, or CDH.

Dissolved oxygen saturation controls PAH biodegradation in freshwater estuary sediments.

Polycyclic aromatic hydrocarbons (PAHs) are common contaminants in terrestrial and aquatic environments and can represent a significant constituent of the carbon pool in coastal sediments. We report here the results of an 18-month seasonal study of PAH biodegradation and heterotrophic bacterial production and their controlling biogeochemical factors from 186 sediment samples taken in a tidally influenced freshwater estuary. For each sampling event, measurements were averaged from 25-45 stations covering approximately 250 km(2). There was a clear relationship between bacterial production and ambient temperature, but none between production and bottom water dissolved oxygen (DO) % saturation or PAH concentrations. In contrast with other studies, we found no effect of temperature on the biodegradation of naphthalene, phenanthrene, or fluoranthene. PAH mineralization correlated with bottom water DO saturation above 70% (r(2) > 0.99). These results suggest that the proportional utilization of PAH carbon to natural organic carbon is as much as three orders of magnitude higher during cooler months, when water temperatures are lower and DO % saturation is higher. Infusion of cooler, well-oxygenated water to the water column overlying contaminated sediments during the summer months may stimulate PAH metabolism preferentially over non-PAH organic matter.

The relationship between age and process of care and patient tolerance of bronchoscopy.

OBJECTIVES: To determine whether patient age is associated with differences in flexible bronchoscopy technique and tolerance. DESIGN: Prospective cohort study. SETTING: University hospital system. PARTICIPANTS: One thousand three hundred fifty-eight adults, including 219 (16.1%) aged 70 and older, undergoing bronchoscopy. MEASUREMENTS: Indications, sampling procedures, medication doses, patient reports of pain, willingness to return, and adverse events associated with bronchoscopy. RESULTS: Indications for bronchoscopy varied with age, with solitary pulmonary nodule (P <.001), mass (P <.001), or lymphadenopathy (P <.001) being more common in older patients. Invasive sampling methods were used more often with increasing age, but variation in disease processes between age groups accounted for the difference in sampling method performed. Mean doses of midazolam and fentanyl given for sedation decreased with increasing age (P <.001). There was no significant difference between older and younger patients in reported very good to excellent pain control (50% of patients >/=70 vs 64% of patients <40; P =.56) or in willingness to return for repeat bronchoscopy (98% vs 92%, respectively; P =.324). Overall risk for an adverse event increased with increasing patient age (P <.01), but adverse events were uncommon and generally not severe. Hypotension and pneumothorax were rare but occurred more often in older persons (1.9% and 3.4% in patients >/=70 vs 0.5% and 0.7% in patients <40, respectively). CONCLUSION: Despite more-invasive sampling methods and less sedation during bronchoscopy, elderly patients tolerate bronchoscopy as well as younger patients. There is increased risk for adverse events with increasing age, but the absolute frequency is low, suggesting that chronological age should not be a contraindication for bronchoscopy in older persons.