Evaluation of PVC and PTFE filters for direct-on-filter crystalline silica quantification by FTIR.

Direct-on-Filter (DoF) analysis of respirable crystalline silica (RCS) by Fourier Transform Infrared (FTIR) spectroscopy is a useful tool for assessing exposure risks. With the RCS exposure limits becoming lower, it is important to characterize and reduce measurement uncertainties. This study systematically evaluated two filter types (i.e., polyvinyl chloride [PVC] and polytetrafluoroethylene [PTFE]) for RCS measurements by DoF FTIR spectroscopy, including the filter-to-filter and day-to-day variability of blank filter FTIR reference spectra, particle deposition patterns, filtration efficiencies, and pressure drops. For PVC filters sampled at a flow rate of 2.5 L/min for 8 h, the RCS limit of detection (LOD) was 7.4 µg/m3 when a designated laboratory reference filter was used to correct the absorption by the filter media. When the spectrum of the pre-sample filter (blank filter before dust sampling) was used for correction, the LOD could be up to 5.9 µg/m3. The PVC absorption increased linearly with reference filter mass, providing a means to correct the absorption differences between the pre-sample and reference filters. For PTFE, the LODs were 12 and 1.2 µg/m3 when a designated laboratory blank or the pre-sample filter spectrum was used for blank correction, respectively, indicating that using the pre-sample blank spectrum will reduce RCS quantification uncertainty. Both filter types exhibited a consistent radially symmetric deposition pattern when particles were collected using 3-piece cassettes, indicating that RCS can be quantified from a single measurement at the filter center. The most penetrating aerodynamic diameters were around 0.1 µm with filtration efficiencies ≥ 98.8% across the measured particle size range with low-pressure drops (0.2-0.3 kPa) at a flow rate of 2.5 L/min. This study concludes that either the PVC or the PTFE filters are suitable for RCS analysis by DoF FTIR, but proper methods are needed to account for the variability of blank absorption among different filters.

The genomic and evolutionary landscapes of anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

Factors Associated with Inhaled Bronchodilator and Oral Corticosteroid Use in Young Children with First Lower Respiratory Tract Infection.

OBJECTIVES: To examine factors associated with claims for and potential overuse of inhaled bronchodilators (IBs) and oral corticosteroids (OCSs) for children <2 years old at first lower respiratory tract infections (LRTIs). STUDY DESIGN: Retrospective cohort study using Colorado All Payer Claims data from 2009 through 2019. Children with asthma were excluded. Primary outcomes were 1) IB and 2) OCS claims within 7 days of index LRTI. Primary predictors were previous IB or OCS claims for each outcome respectively. Covariates included demographics, atopy, family history of asthma, complex chronic conditions, prior inhaled corticosteroid claim, and location of index LRTI. Separate multivariable logistic regression models were used for each outcome. RESULTS: Of 10 194 eligible children, 1468 (14.4%) had an IB and 741 (7.3%) an OCS claim at or within 7 days of index LRTI. Index LRTIs were most often at outpatient visits (64%). Adjusting for covariates, prior IB prescription was associated with the IB outcome (aOR 1.9; 95% CI 1.3, 2.8), and prior OCS prescription was associated with the OCS outcome (AOR 2.2; 95% CI 1.7, 2.9). Other variables associated with either outcome included age, sex, insurance, location, and atopy. Prior inhaled corticosteroid claim, asthma family history, and complex chronic conditions were not associated with either outcome. CONCLUSIONS: This study identifies factors that might serve as opportunities for de-implementation strategies for IB and OCS overuse in young children with LRTI.

Contributions of non-tailpipe emissions to near-road PM2.5 and PM10: A chemical mass balance study.

As the importance of non-tailpipe particles (NTP) over tailpipe emissions from urban traffic has been increasing, there is a need to evaluate NTP contributions to ambient particulate matter (PM) using representative source profiles. The Brake and Tire Wear Study conducted in Los Angeles, California in the winter of 2020 collected 64 PM2.5 and 64 PM10 samples from 32 pairs of downwind-upwind measurements at two near-road locations (I-5 in Anaheim and I-710 in Long Beach). These samples were characterized for inorganic and organic markers and, along with locally-developed brake wear, tire wear, and road dust source profiles, subject to source apportionment using the effective-variance chemical mass balance (EV-CMB) model. Model results highlighted the dominance of resuspended dust in both PM2.5 (23-33%) and PM10 (32-53%). Brake and tire wear contributed more to PM2.5 than tailpipe exhausts (diesel + gasoline) for I-5 (29-30% vs. 19-21%) while they were comparable for I-710 (15-17% vs. 15-19%). For PM10, the brake and tire wear contributions were 2-3 times the exhaust contributions. Different fleet compositions on and near I-5 and I-710 appeared to influence the relative importance of NTP and exhaust sources. The downwind-upwind differences in source contributions were often insignificant, consistent with small and/or nearly equal impacts of adjacent highway traffic emissions on the downwind and upwind sites. The utility of sole markers, such as barium and zinc, to predict brake and tire wear abundances in ambient PM is evaluated.

Geriatric Intertrochanteric Fractures: What Is the Optimal Follow-Up Period?

OBJECTIVE: Evaluate patients with intertrochanteric fractures who were treated operatively to determine optimal follow-up to ensure complete fracture healing and recognize complications. DESIGN: Retrospective review. SETTING: Academic Level 1 trauma center. PATIENTS/PARTICIPANTS: Inclusion criteria included isolated intertroch fractures (not pathologic) and complete radiographic and clinical data, with at least 1-year follow-up. Four hundred ninety-seven patients were identified. Two hundred forty-nine patients met inclusion criteria with 194 patients studied. INTERVENTION: Operative fixation with either CMN or SHS. MAIN OUTCOME MEASUREMENTS: Radiographic parameters included time to union, neck-shaft angle, tip apex distance, and femoral neck screw telescoping (shortening) for both CMS and SHS combined. Postoperative complications were recorded. RESULTS: Union was achieved at a mean of 64.8 ± 30.7 days. Mortality (n = 12), infection (n = 4), and implant failure (n = 5) occurred within 3 months. Neck-shaft angle was changed before 3 months. Significant neck shortening for both CMN and SHS occurred within 6 weeks ( P =<0.001). Major complications occurred early, within 3 months. CONCLUSIONS: Most fractures healed by 3 months and the remainder by 6 months. Routine follow-up for 6 months is more than sufficient for most of these fractures. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Multimodal image and spectral feature learning for efficient analysis of water-suspended particles.

We have developed a method to combine morphological and chemical information for the accurate identification of different particle types using optical measurement techniques that require no sample preparation. A combined holographic imaging and Raman spectroscopy setup is used to gather data from six different types of marine particles suspended in a large volume of seawater. Unsupervised feature learning is performed on the images and the spectral data using convolutional and single-layer autoencoders. The learned features are combined, where we demonstrate that non-linear dimensional reduction of the combined multimodal features can achieve a high clustering macro F1 score of 0.88, compared to a maximum of 0.61 when only image or spectral features are used. The method can be applied to long-term monitoring of particles in the ocean without the need for sample collection. In addition, it can be applied to data from different types of sensor measurements without significant modifications.

Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects.

PURPOSE: Superficial siderosis, a progressive, debilitating, neurological disease, often presents with bilateral impairment of auditory and vestibular function. We highlight that superficial siderosis is often due to a repairable spinal dural defect of the type that can also cause spontaneous intracranial hypotension. METHODS: Retrospective chart review of five patients presenting with moderate to severe, progressive bilateral sensorineural hearing loss as well as vestibular loss. All patients had developed superficial siderosis from spinal dural defects: three after trauma, one after spinal surgery and one from a thoracic discogenic microspur. RESULTS: The diagnosis was made late in all five patients; despite surgical repair in four, hearing and vestibular loss failed to improve. CONCLUSIONS: In patients presenting with progressive bilateral sensorineural hearing loss, superficial siderosis should be considered as a possible cause. If these patients also have bilateral vestibular loss, cerebellar impairment and anosmia, then the diagnosis is likely and the inevitable disease progress might be halted by finding and repairing the spinal dural defect.

Evidence of non-tailpipe emission contributions to PM2.5 and PM10 near southern California highways.

Particulate Matter (PM) concentrations near highways are influenced by vehicle tailpipe and non-tailpipe emissions, other emission sources, and urban background aerosols. This study collected PM2.5 and PM10 filter samples near two southern California highways (I-5 and I-710) over two weeks in winter 2020. Samples were analyzed for chemical source markers. Mean PM2.5 and PM10 concentrations were approximately 10-15 and 30 µg/m3, respectively. Organic matter, mineral dust, and elemental carbon (EC) were the most abundant PM components. EC and polycyclic aromatic hydrocarbons at I-710 were 19-26% and 47% higher than those at the I-5 sites, respectively, likely due to a larger proportion of diesel vehicles. High correlations were found for elements with common sources, such as markers for brake wear (e.g., Fe, Ba, Cu, and Zr) and road dust (e.g., Al, Si, Ca, and Mn). Based on rubber abundances, the contributions of tire tread particles to PM2.5 and PM10 mass were approximately 8.0% at I-5 and 5.5% at I-710. Two different tire brands showed significantly different Si, Zn, carbon, and natural rubber abundances.

Modified Masquelet Technique and Primary Tibial Metaphyseal Shortening for the Management of Proximal Tibial-infected Non-union in a Patient with Alcohol-induced Neuropathy: A Case Study.

Aim: To highlight the role of the Masquelet technique as a limb salvage procedure for a neuropathic patient presenting with infected non-union of proximal tibia. Background: The management of an infected non-union in neuropathic patients is most challenging; with various treatment options available, the prognosis is often guarded. Case description: A 37-year-old male with chronic polyneuropathy, also possessing a contralateral midfoot Charcot arthropathy secondary to a history of alcohol abuse, developed infection after a proximal tibial osteotomy for a preceding mal-non-union of a proximal tibia fracture. The management included hardware removal, excision of necrotic bone, interim insertion of antibiotic-loaded bone cement followed by an acute shortening and revision of the internal fixation utilising a second surgical incision. Successful bone union and eradication of infection was achieved and maintained after 13 months follow-up. Conclusion: A successful outcome was achieved for an infected non-union of a long bone in a neuropathic patient using the Masquelet technique which was then followed with a second-stage removal of the spacer and shortening. By performing the revision ORIF surgery utilising a different skin incision in the setting of complicated previous surgical scars proved to be a viable technique towards reducing risk of recurrence of infection and a good outcome. Clinical significance: Utilisation of the Masquelet technique and limb shortening in a staged manner for the management of long bone infections in neuropathic patients has not been reported before and may be valuable in such demanding clinical situations. How to cite this article: Mahmoud AN, Watson JT, Horwitz DS. Modified Masquelet Technique and Primary Tibial Metaphyseal Shortening for the Management of Proximal Tibial-infected Non-union in a Patient with Alcohol-induced Neuropathy: A Case Study. Strategies Trauma Limb Reconstr 2023;18(3):181-185.

Infectious viral shedding of SARS-CoV-2 Delta following vaccination: A longitudinal cohort study.

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P = 0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.

Spatiotemporal patterns of PFAS in water and crop tissue at a beneficial wastewater reuse site in central Pennsylvania.

Per- and polyfluoroalkyl substances (PFAS) are a collective name for thousands of synthetic compounds produced to enhance consumer and industrial products since the 1940s. They do not easily degrade, and some are known to pose serious ecological and human health concerns at trace concentrations (ng L-1 levels). Per- and polyfluoroalkyl substances persist in treated wastewater and are inadvertently introduced into the environment when treated wastewater is reused as an irrigation source. The Pennsylvania State University (PSU) has been spray-irrigating its wastewater at a 2.45 km2 mixed-use agricultural and forested site known as the "Living Filter" since the 1960s. To understand the spatiotemporal patterns of 20 PFAS at the Living Filter, water samples were collected bimonthly from fall 2019 through winter 2021 from the PSU's wastewater effluent and from each of the site's 13 monitoring wells. Crop tissue was collected at the time of harvest to assess PFAS presence in corn silage and tall fescue grown at the study site. Total measured PFAS concentrations in the monitoring wells ranged from nondectable to 155 ng L-1 , with concentrations increasing with the direction of groundwater flow. Concentrations within each well exhibited little temporal variability across sampling events, with mixed relationships between PFAS and groundwater elevation observed between wells. Further, >84% of the PFAS present in livestock feed crops were short-chain compounds, with PFAS consumed annually by livestock fed crops harvested from the site estimated to be 2.46-7.67 mg animal-1 yr-1 . This research provides insight into the potential impacts of long-term beneficial reuse of treated wastewater on groundwater and crop tissue quality.

A Revised Phylogenetic Classification for Viola (Violaceae).

The genus Viola (Violaceae) is among the 40-50 largest genera among angiosperms, yet its taxonomy has not been revised for nearly a century. In the most recent revision, by Wilhelm Becker in 1925, the then-known 400 species were distributed among 14 sections and numerous unranked groups. Here, we provide an updated, comprehensive classification of the genus, based on data from phylogeny, morphology, chromosome counts, and ploidy, and based on modern principles of monophyly. The revision is presented as an annotated global checklist of accepted species of Viola, an updated multigene phylogenetic network and an ITS phylogeny with denser taxon sampling, a brief summary of the taxonomic changes from Becker's classification and their justification, a morphological binary key to the accepted subgenera, sections and subsections, and an account of each infrageneric subdivision with justifications for delimitation and rank including a description, a list of apomorphies, molecular phylogenies where possible or relevant, a distribution map, and a list of included species. We distribute the 664 species accepted by us into 2 subgenera, 31 sections, and 20 subsections. We erect one new subgenus of Viola (subg. Neoandinium, a replacement name for the illegitimate subg. Andinium), six new sections (sect. Abyssinium, sect. Himalayum, sect. Melvio, sect. Nematocaulon, sect. Spathulidium, sect. Xanthidium), and seven new subsections (subsect. Australasiaticae, subsect. Bulbosae, subsect. Clausenianae, subsect. Cleistogamae, subsect. Dispares, subsect. Formosanae, subsect. Pseudorupestres). Evolution within the genus is discussed in light of biogeography, the fossil record, morphology, and particular traits. Viola is among very few temperate and widespread genera that originated in South America. The biggest identified knowledge gaps for Viola concern the South American taxa, for which basic knowledge from phylogeny, chromosome counts, and fossil data is virtually absent. Viola has also never been subject to comprehensive anatomical study. Studies into seed anatomy and morphology are required to understand the fossil record of the genus.

Impacts of the COVID-19 pandemic on pharmaceuticals in wastewater treated for beneficial reuse: Two case studies in central Pennsylvania.

During the COVID-19 pandemic, wastewater surveillance was leveraged as a powerful tool for monitoring community-scale health. Further, the well-known persistence of some pharmaceuticals through wastewater treatment plants spurred concerns that increased usage of pharmaceuticals during the pandemic would increase the concentrations in wastewater treatment plant effluent. We collected weekly influent and effluent samples from May 2020 through May 2021 from two wastewater treatment plants in central Pennsylvania, the Penn State Water Reclamation Facility and the University Area Joint Authority, that provide effluent for beneficial reuse, including for irrigation. Samples were analyzed for severe acute respiratory syndrome coronavirus 2 (influent only), two over-the-counter medicines (acetaminophen and naproxen), five antibiotics (ampicillin, doxycycline, ofloxacin, sulfamethoxazole, and trimethoprim), two therapeutic agents (remdesivir and dexamethasone), and hydroxychloroquine. Although there were no correlations between pharmaceutical and virus concentration, remdesivir detection occurred when the number of hospitalized patients with COVID-19 increased, and dexamethasone detection co-occurred with the presence of patients with COVID-19 on ventilators. Additionally, Penn State decision-making regarding instruction modes explained the temporal variation of influent pharmaceutical concentrations, with detection occurring primarily when students were on campus. Risk quotients calculated for pharmaceuticals with known effective and lethal concentrations at which 50% of a population is affected for fish, daphnia, and algae were generally low in the effluent; however, some acute risks from sulfamethoxazole were high when students returned to campus. Remdesivir and dexamethasone persisted through the wastewater treatment plants, thereby introducing novel pharmaceuticals directly to soils and surface water. These results highlight connections between human health and water quality and further demonstrate the broad utility of wastewater surveillance.

Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children's sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.

Sorption and desorption behavior of four antibiotics at concentrations simulating wastewater reuse in agricultural and forested soils.

Due to rises in antibiotic resistance, fate and transport of antibiotics in soil systems requires greater understanding to determine potential risks to human and animal health. Adsorption coefficients (Kd and Kf) are standard measures for determining sorption capacity and partitioning behavior of organic contaminants in solid matrices. Frequently, sorption studies use higher antibiotic concentrations (mg L-1) and larger spiked water volume to mass of soil (>5:1), which may not reflect sorption behaviors of antibiotics at low concentrations (ng L-1 - µg L-1) in natural soils. The aim of this study was to determine sorption and desorption behaviors of four antibiotics commonly found in soils due to wastewater reuse using parameters replicating typical soil conditions. Concentrations (µg L-1) of sulfamethoxazole (SMX), trimethoprim (TMP), lincomycin (LIN) and ofloxacin (OFL) were equilibrated with four soil types at a 2:1 ratio of spiked water volume to mass of soil, which better represents field conditions. Log Kf and log Kfoc value ranges in this study were 1.88-1.95 and 3.2-4.7 for TMP, 0.43-1.4 and 2.7-3.2 for SMX, and 0.65-1.4 and 2.0-4.1 for LIN, respectively. Ofloxacin adsorbed tightly to soil particles, and adsorption coefficients could not be calculated. Sorption values were higher than previous studies that used similar soil types but had higher ratios of spiking solution to mass of soil (>5:1). Overall, OFL and TMP are expected to strongly interact with soil particles and be less mobile, while SMX and LIN are expected to be more mobile due to weaker sorption interactions.

Review of Filters for Air Sampling and Chemical Analysis in Mining Workplaces.

This review considers the use of filters to sample air in mining workplace environments for dust concentration measurement and subsequent analysis of hazardous contaminants, especially respirable crystalline silica (RCS) on filters compatible with wearable personal dust monitors (PDM). The review summarizes filter vendors, sizes, costs, chemical and physical properties, and information available on filter modeling, laboratory testing, and field performance. Filter media testing and selection should consider the characteristics required for mass by gravimetry in addition to RCS quantification by Fourier-transform infrared (FTIR) or Raman spectroscopic analysis. For mass determination, the filters need to have high filtration efficiency (≥99% for the most penetrable particle sizes) and a reasonable pressure drop (up to 16.7 kPa) to accommodate high dust loading. Additional requirements include: negligible uptake of water vapor and gaseous volatile compounds; adequate particle adhesion as a function of particle loading; sufficient particle loading capacity to form a stable particle deposit layer during sampling in wet and dusty environments; mechanical strength to withstand vibrations and pressure drops across the filter; and appropriate filter mass compatible with the tapered element oscillating microbalance. FTIR and Raman measurements require filters to be free of spectral interference. Furthermore, because the irradiated area does not completely cover the sample deposit, particles should be uniformly deposited on the filter.

Comparison of POCIS and grab sampling techniques for monitoring PPCPs in vernal pools in central Pennsylvania.

Active ingredients in pharmaceuticals and personal care products (PPCPs) can persist through wastewater treatment plants and be released into the environment where they can inadvertently pose risks to non-target organisms. Emerging contaminants (ECs), including PPCPs, are commonly detected in wastewater effluent. With the increasing beneficial re-use of treated wastewater globally, there is a need to understand how spray-irrigation activities affect the occurrence and persistence of ECs in the environment to which they are introduced. Here, we explore the impacts of wastewater spray-irrigation on nearby ephemeral wetlands (e.g., vernal pools) through the use of grab and Polar Organic Chemical Integrative Sampling (POCIS) techniques. This study sought to determine whether integrative sampling techniques are better suited than traditional grab sampling techniques in assessing the presence and concentrations of ECs in vernal pools by evaluating 34 ECs in six vernal pools in central Pennsylvania. Three pools were impacted by wastewater spray-irrigation activities and three were in a nearby forested area. Results of this study found that POCIS detected a wide range of 25 ECs (log Kow between -2.6 and 9.37) more or, in some cases, equally frequently, relative to grab samples. Additionally, grab samples were found to best capture short-lived elevated inputs of ECs (from irrigation events) while POCIS were found to best capture ECs that were present in vernal pools over a longer period of time (weeks to months). For ECs detected more frequently in grab samples, concentrations were higher compared to time weighted average aqueous concentrations estimated from POCIS. This study advances understanding of the potential impact of wastewater beneficial reuse on vernal pools and informs how best to monitor the presence of ECs in vernal pools using integrative and grab sampling techniques.

Association between early childhood lower respiratory tract infections and subsequent asthma.

OBJECTIVE: We examined the relationship between recurrent lower respiratory tract infections (LRTI) in young children and subsequent childhood asthma outcomes. METHODS: Retrospective cohort study using 2009-2017 Colorado All Payer Claims Database to assess 0- to 2-year-old children with visits due to LRTI and acute gastroenteritis (AGE). The primary exposure was number of LRTI visits prior to 2 years of age. Children with AGE served as the no LRTI comparator group. The primary outcome was incident asthma, defined by ICD-9 (490.XX) or ICD-10 (J45.9XX) codes, in the same children between 3 and 9 years of age. Multivariable accelerated failure time (AFT) models were used to estimate the effect of LRTI visits on median time to asthma diagnosis. Sensitivity analyses were performed using more conservative asthma diagnostic criteria and with hospitalized children only. RESULTS: Of 38,441 eligible subjects, 32,729 had ≥1 LRTI and 5,712 had AGE (no LRTI) between 0 and 2 years of age. Children with ≥3 LRTI visits had an 80% decrease in median time to asthma diagnosis relative to those with AGE visits only (time ratio [TR] 0.2; 95% CI 0.16, 0.24). Children with ≥3 LRTI hospitalizations had a 98% reduction in median time to asthma diagnosis relative to those with AGE hospitalizations only (TR 0.02; 95% CI 0.01, 0.07). History of atopy, wheezing, and family history of asthma documented prior to 2 years of age were also associated with earlier asthma diagnosis. CONCLUSIONS: Recurrent LRTIs, especially LRTI hospitalizations, before 2 years of age are associated with earlier diagnosis of pediatric asthma.