Measuring lung diffusing capacity: an opportunity for improved medical surveillance and disability evaluation of coal miners.

OBJECTIVES: Spirometry is the primary lung function test utilised for medical surveillance and disability examination for coal mine dust lung disease. However, spirometry likely underestimates physiologic impairment. We sought to characterise abnormalities of single-breath diffusing capacity for carbon monoxide (DLCO) among a population of former coal miners. METHODS: Data from 3115 former coal miners evaluated at a West Virginia black lung clinic between 2006 and 2015 were retrospectively analysed to study the association between diffusion impairment (abnormally low DLCO), resting spirometry and the presence and severity of coal workers' pneumoconiosis on chest radiography. We developed ordinary least squares linear regression models to evaluate factors associated with per cent predicted DLCO (DLCOpp). RESULTS: Diffusion impairment was identified in 20.2% of subjects. Ten per cent of all miners with normal spirometry had diffusion impairment including 7.4% of never smokers. The prevalence of diffusion impairment increased with worsening radiographic category of pneumoconiosis. Mean DLCOpp decreased with increasing small opacity profusion subcategory in miners without progressive massive fibrosis. Linear regression analysis also showed significant decreases in DLCOpp with increasing small opacity profusion and presence of large opacities. CONCLUSIONS: Diffusion impairment is common among former coal miners, including among never smokers, miners without radiographic pneumoconiosis and miners with normal spirometry. These findings demonstrate the value of including DLCO testing in disability examinations of former coal miners and an important role for its use in medical surveillance of working miners to detect early chronic lung disease.

Resting diffusing capacity and severity of radiographic disease predict gas exchange abnormalities with exercise in former US coal miners.

BACKGROUND: The US Department of Labor (DOL) does not fund diffusing capacity (DLCO) or metabolic measurements from cardiopulmonary exercise testing (CPET) for coal miners' disability evaluations. Although exercise arterial blood gas testing is covered, many miners are unable to perform maximal tests, and sampling at peak exercise can be challenging. We explored the relationship between resting DLCO, radiographic disease severity, and CPET abnormalities in former US coal miners. METHODS: We analyzed data from miners evaluated between 2005 and 2015. Multivariable linear and logistic regression analyses were used to examine relationships between percent predicted (pp) forced expiratory volume in 1 s (FEV1pp), DLCOpp, VO2maxpp, A-a oxygen gradient (A-a)pp, dead space fraction (Vd/Vt), disabling oxygen tension (PO2), and radiographic findings of pneumoconiosis. RESULTS: Data from 2015 male coal miners was analyzed. Mean tenure was 28 years (SD 8.6). Thirty-twopercent had an abnormal A-a gradient (>150 pp), 20% had elevated Vd/Vt (>0.33), and 34% a VO2max < 60 pp. DLCOpp strongly predicted a disabling PO2, with an odds ratio (OR) of 2.33 [2.09-2.60], compared to 1.18 [1.08-1.29] for FEV1. Each increase in subcategory of small opacity (simple) pneumoconiosis increased the odds of a disabling PO2 by 42% [1.29-1.57], controlling for age, body mass index, pack-years of tobacco smoke exposure, and years of coal mine employment. CONCLUSIONS: DLCO is the best resting pulmonary function test predictor of CPET abnormalities. Radiographic severity of pneumoconiosis was also associated with CPET abnormalities. These findings support funding DLCO testing for impairment and suggest the term "small opacity" should replace "simple" pneumoconiosis to reflect significant associations with impairment.

Historical shift in pathological type of progressive massive fibrosis among coal miners in the USA.

BACKGROUND: Pneumoconiosis among coal miners in the USA has been resurgent over the past two decades, despite modern dust controls and regulatory standards. Previously published studies have suggested that respirable crystalline silica (RCS) is a contributor to this disease resurgence. However, evidence has been primarily indirect, in the form of radiographic features. METHODS: We obtained lung tissue specimens and data from the National Coal Workers' Autopsy Study. We evaluated specimens for the presence of progressive massive fibrosis (PMF) and used histopathological classifications to type these specimens into coal-type, mixed-type and silica-type PMF. Rates of each were compared by birth cohort. Logistic regression was used to assess demographic and mining characteristics associated with silica-type PMF. RESULTS: Of 322 cases found to have PMF, study pathologists characterised 138 (43%) as coal-type, 129 (40%) as mixed-type and 55 (17%) as silica-type PMF. Among earlier birth cohorts, coal-type and mixed-type PMF were more common than silica-type PMF, but their rates declined in later birth cohorts. In contrast, the rate of silica-type PMF did not decline in cases from more recent birth cohorts. More recent year of birth was significantly associated with silica-type PMF. CONCLUSIONS: Our findings demonstrate a shift in PMF types among US coal miners, from a predominance of coal- and mixed-type PMF to a more commonly encountered silica-type PMF. These results are further evidence of the prominent role of RCS in the pathogenesis of pneumoconiosis among contemporary US coal miners.

Prenatal exposure to poly- and perfluoroalkyl substances and the incidence of asthma in early childhood.

EXPOSURE TO POLY: and perfluoroalkyl substances (PFAS) in early life may increase the risk of childhood asthma, but evidence has been inconsistent. We estimated associations between maternal serum concentrations of PFAS during pregnancy and clinician-diagnosed asthma incidence in offspring through age eight. We included 597 mother-child pairs with PFAS quantified in mid-pregnancy serum and childhood medical records reviewed for asthma diagnoses. We used separate Cox proportional hazards models to assess the relationship between log-transformed concentrations of five PFAS and the incidence of asthma. We estimated associations between the PFAS mixture and clinician-diagnosed asthma incidence using quantile-based g-computation. PFAS concentrations were similar to those among females in the US general population. Seventeen percent of children (N = 104) were diagnosed with asthma during follow-up. Median (interquartile range) duration of follow-up was 4.7 (4.0, 6.2) years, and median age at asthma diagnosis was 1.7 (0.9, 2.8) years. All adjusted hazard ratios (HRs) were elevated, but all 95% confidence intervals (CI) included the null. The HR (95% CI) of asthma for a one-quartile increase in the PFAS mixture was 1.17 (0.86, 1.61). In this cohort of children followed to eight years of age, prenatal PFAS concentrations were not significantly associated with incidence of clinician-diagnosed asthma.

Deployment-Related Respiratory Disease: Where Are We?

Military personnel and veterans who have deployed to Afghanistan, Iraq, and parts of Southwest Asia (SWA) since 1990 are at risk of developing a host of respiratory symptoms and deployment-related respiratory diseases (DRRDs). This review aims to summarize our current understanding of DRRD and inform pulmonary practitioners of recent updates to DRRD screening, diagnosis, evaluation, and management. The most common respiratory diseases in these patients include asthma, chronic sinonasal disease, laryngeal disease/dysfunction, and distal lung disease. Pulmonary function testing and chest imaging are the most commonly used diagnostic tools, but techniques such as lung clearance index testing via multiple breath washout, forced oscillation testing/impulse oscillometry, and quantitative chest computed tomography (CT) assessment appear promising as noninvasive modalities to aid in lung disease detection in this population. We also summarize guidance on conducting an occupational and deployment exposure history as well as recommendations for testing. Finally, we discuss the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act of 2022 (PACT Act) that includes a list of health conditions that are "presumptively" considered to be related to SWA military deployment toxic exposures, and provide resources for clinicians who evaluate and treat patients with DRRD.

Prevalence and severity of abnormal lung function among US former coal miners with and without radiographic coal workers' pneumoconiosis.

OBJECTIVES: Examination of lung function abnormalities among coal miners has historically focused on actively working miners. This likely underestimates the true burden of chronic respiratory disease. The objective of this study was to characterise patterns and severity of lung function impairment among a population of former coal miners. METHODS: Cross-sectional data from 2568 former coal miners evaluated at eight US Black Lung clinics in a 12-month period were retrospectively analysed for patterns of prebronchodilator spirometric abnormality and severity of lung function impairment. Spirometry data from a subset of former miners with chest radiographs were analysed based on the presence and severity of coal workers' pneumoconiosis (CWP). RESULTS: Abnormal spirometry was identified in 56.6% of subjects. The age-standardised prevalence of airflow obstruction among miners aged ≥45 years was 18.9% overall and 12.2% among never smokers. Among 1624 subjects who underwent chest radiography, the prevalence and severity of abnormal spirometry increased with worsening radiographic category for pneumoconiosis. Of never-smoking former miners without radiographic CWP, 39.0% had abnormal spirometry; 25.1% had abnormally low forced expiratory volume in 1 s (FEV1), and 17.1% had moderate to severe FEV1 impairment. CONCLUSIONS: Abnormal spirometry is common among former coal miners. While ever-smoking former miners had higher rates of airflow obstruction, never-smoking former miners also demonstrated clinically significant airflow obstruction, including those without radiographic pneumoconiosis. These findings demonstrate the importance of recognising physiological as well as imaging manifestations of coal mine dust lung diseases in former miners.

Demographic, exposure and clinical characteristics in a multinational registry of engineered stone workers with silicosis.

OBJECTIVES: To investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry. METHODS: With ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher's exact tests and logistic regression. RESULTS: Among 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity. CONCLUSIONS: Findings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.

Quantitative imaging analysis detects subtle airway abnormalities in symptomatic military deployers.

BACKGROUND: Exposure to inhalational hazards during post-9/11 deployment to Southwest Asia and Afghanistan puts military personnel at risk for respiratory symptoms and disease. Pulmonary function and qualitative chest high resolution computed tomography (HRCT) are often normal in "deployers" with persistent respiratory symptoms. We explored the utility of quantitative HRCT imaging markers of large and small airways abnormalities, including airway wall thickness, emphysema, and air trapping, in symptomatic deployers with clinically-confirmed lung disease compared to controls. METHODS: Chest HRCT images from 45 healthy controls and 82 symptomatic deployers with asthma, distal lung disease or both were analyzed using Thirona Lung quantification software to calculate airway wall thickness (by Pi10), emphysema (by percentage of lung volume with attenuation < -950 Hounsfield units [LAA%-950]), and three parameters of air trapping (expiratory/inspiratory total lung volume and mean lung density ratios, and LAA%-856). SAS v.9.4 was used to compare demographic and clinical characteristics between deployers and controls using Chi-Square, Fisher Exact or t-tests. Linear regression was used to assess relationships between pulmonary function and quantitative imaging findings. RESULTS: Gender and smoking status were not statistically significantly different between groups, but deployers were significantly younger than controls (42 vs 58 years, p < 0.0001), had higher body mass index (31 vs 28 kg/m2, p = 0.01), and had fewer total smoking pack-years (8 vs. 26, p = 0.007). Spirometric measures were not statistically significantly different between groups. Pi10 and LAA%-950 were significantly elevated in deployers compared to controls in unadjusted analyses, with the emphysema measure remaining significantly higher in deployers after adjustment for age, sex, smoking, BMI, and expiratory total lung volume. Air trapping parameters were more common in control images, likely due to differences in age and smoking between groups. Among deployers, LAA%-950 and Pi10 were significantly correlated with spirometric markers of obstruction based on ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) and/or percent predicted FEV1. CONCLUSIONS: Quantitative chest HRCT imaging analysis identifies emphysema in deployers with asthma and distal lung disease, and may be useful in detecting and monitoring deployment-related lung disease in a population where spirometry is typically normal.

Severe Silicosis in Engineered Stone Fabrication Workers - California, Colorado, Texas, and Washington, 2017-2019.

Silicosis is an incurable occupational lung disease caused by inhaling particles of respirable crystalline silica. These particles trigger inflammation and fibrosis in the lungs, leading to progressive, irreversible, and potentially disabling disease. Silica exposure is also associated with increased risk for lung infection (notably, tuberculosis), lung cancer, emphysema, autoimmune diseases, and kidney disease (1). Because quartz, a type of crystalline silica, is commonly found in stone, workers who cut, polish, or grind stone materials can be exposed to silica dust. Recently, silicosis outbreaks have been reported in several countries among workers who cut and finish stone slabs for countertops, a process known as stone fabrication (2-5). Most worked with engineered stone, a manufactured, quartz-based composite material that can contain >90% crystalline silica (6). This report describes 18 cases of silicosis, including the first two fatalities reported in the United States, among workers in the stone fabrication industry in California, Colorado, Texas, and Washington. Several patients had severe progressive disease, and some had associated autoimmune diseases and latent tuberculosis infection. Cases were identified through independent investigations in each state and confirmed based on computed tomography (CT) scan of the chest or lung biopsy findings. Silica dust exposure reduction and effective regulatory enforcement, along with enhanced workplace medical and public health surveillance, are urgently needed to address the emerging public health threat of silicosis in the stone fabrication industry.

Longitudinal changes in lung function following post-9/11 military deployment in symptomatic veterans.

RATIONALE: Exposure to burn pit smoke, desert and combat dust, and diesel exhaust during military deployment to Southwest Asia and Afghanistan (SWA) can cause deployment-related respiratory diseases (DRRDs) and may confer risk for worsening lung function after return. METHODS: Study subjects were SWA-deployed veterans who underwent occupational lung disease evaluation (n = 219). We assessed differences in lung function by deployment exposures and DRRD diagnoses. We used linear mixed models to assess changes in lung function over time. RESULTS: Most symptomatic veterans reported high intensity deployment exposure to diesel exhaust and burn pit particulates but had normal post-deployment spirometry. The most common DRRDs were deployment-related distal lung disease involving small airways (DDLD, 41%), deployment-related asthma (DRA, 13%), or both DRA/DDLD (24%). Those with both DDLD/DRA had the lowest estimated mean spirometry measurements five years following first deployment. Among those with DDLD alone, spirometry measurements declined annually, adjusting for age, sex, height, weight, family history of lung disease, and smoking. In this group, the forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) ratio declined 0.2% per year. Those with more intense inhalational exposure had more abnormal lung function. We found significantly lower estimated FVC and total lung capacity five years following deployment among active duty participants (n = 173) compared to those in the reserves (n = 26). CONCLUSIONS: More intense inhalational exposures were linked with lower post-deployment lung function. Those with distal lung disease (DDLD) experienced significant longitudinal decline in FEV1/FVC ratio, but other DRRD diagnosis groups did not.

Particle Morphology and Elemental Analysis of Lung Tissue from Post-9/11 Military Personnel with Biopsy-Proven Lung Disease.

The relationship between exposure to inhaled inorganic particulate matter and risk for deployment-related lung disease in military personnel is unclear due in part to difficulties characterizing individual exposure to airborne hazards. We evaluated the association between self-reported deployment exposures and particulate matter (PM) contained in lung tissue from previously deployed personnel with lung disease ("deployers"). The PM in deployer tissues was compared to normal lung tissue PM using the analytical results of scanning electron microscopy and inductively coupled plasma mass spectrometry. The majority of PM phases for both the deployers and the controls were sub-micrometer in size and were compositionally classified as aluminum and zirconium oxides, carbonaceous particles, iron oxides, titanium oxides, silica, other silicates, and other metals. The proportion of silica and other silicates was significantly higher in the retained dust from military veterans with biopsy-confirmed deployment-related lung disease compared to the control subjects. Within the deployer population, those who had combat jobs had a higher total PM burden, though the difference was not statistically significant. These findings have important implications for understanding the role of inhaled inorganic dusts in the risk for lung injury in previously deployed military veterans.

Racial Differences in Respiratory Impairment, Pneumoconiosis, and Federal Compensation for Western U.S. Indigenous Coal Miners.

Rationale: Indigenous populations in the United States face numerous health disparities, but the health of Indigenous workers is less well understood. In a recent surveillance study of active Indigenous coal miners, 3% had coal workers' pneumoconiosis/black lung, and 9% had respiratory impairment. However, occupational lung disease prevalence among Indigenous coal miners has not been directly compared with that among other race/ethnicity groups. Coal miners who are totally disabled from black lung may qualify for U.S. Department of Labor (DOL) compensation benefits, but it is unclear how current federal spirometry criteria affect qualification for Indigenous coal miners.Objectives: To compare findings of pneumoconiosis and respiratory impairment in Indigenous and non-Indigenous coal miners in the western United States and assess federal compensation qualification for Indigenous miners using different spirometry standards.Methods: We used voluntary medical surveillance data from 2002 to 2023 to compare the adjusted odds of pneumoconiosis and respiratory impairment between Indigenous/non-Indigenous coal miners. We examined the proportion of Indigenous miners meeting DOL criteria for federal compensation using different spirometry standards.Results: We identified 691 western U.S. coal miners with at least one year of coal mining employment, 289 Indigenous and 402 non-Indigenous (96% White/Hispanic). Indigenous miners had a greater odds ratio for pneumoconiosis for each additional decade of life (2.47 [95% confidence interval (CI), 1.66-3.68]) compared with non-Indigenous coal miners (1.48 [95% CI, 1.19-1.85]). For each decade, Indigenous coal miners also had a greater adjusted odds ratio for respiratory impairment (1.67 [95% CI, 1.25-2.24]) than non-Indigenous miners (1.06 [95% CI, 0.90-1.25]). Indigenous miners had an additional decline of 71 ml (95% CI, 6-136 ml) in forced expiratory volume in 1 second for each decade of life compared with non-Indigenous coal miners. Using the DOL-mandated Knudson (1976) spirometry standard rather than an Indigenous-specific standard, 6 of 18 (33%) Indigenous miners would not qualify for federal compensation.Conclusions: Indigenous coal miners experience greater adjusted odds for pneumoconiosis and respiratory impairment per decade of life and greater decline in forced expiratory volume in 1 second despite lower smoking rates. Structural inequities exist in federal spirometry requirements for Indigenous miners seeking DOL black lung benefits. Regulatory reform is needed to address barriers to compensation for these underrepresented workers.

In Situ Lung Dust Analysis by Automated Field Emission Scanning Electron Microscopy With Energy Dispersive X-ray Spectroscopy: A Method for Assessing Inorganic Particles in Lung Tissue From Coal Miners.

CONTEXT.­: Overexposure to respirable coal mine dust can cause severe lung disease including progressive massive fibrosis (PMF). Field emission scanning electron microscopy with energy dispersive x-ray spectroscopy (FESEM-EDS) has been used for in situ lung dust particle analysis for evaluation of disease etiology. Automating such work can reduce time, costs, and user bias. OBJECTIVE.­: To develop and test an automated FESEM-EDS method for in situ analysis of inorganic particles in coal miner lung tissue. DESIGN.­: We programmed an automated FESEM-EDS procedure to collect particle size and elemental data, using lung tissue from 10 underground coal miners with PMF and 4 control cases. A statistical clustering approach was used to establish classification criteria based on particle chemistry. Data were correlated to PMF/non-PMF areas of the tissue, using corresponding brightfield microscopy images. Results for each miner case were compared with a separate corresponding analysis of particles recovered following tissue digestion. RESULTS.­: In situ analysis of miner tissues showed higher particle number densities than controls and densities were generally higher in PMF than non-PMF areas. Particle counts were typically dominated by aluminum silicates with varying percentages of silica. Compared to digestion results for the miner tissues, in situ results indicated lower density of particles (number per tissue volume), larger size, and a lower ratio of silica to total silicates-probably due to frequent particle clustering in situ. CONCLUSIONS.­: Automated FESEM-EDS analysis of lung dust is feasible in situ and could be applied to a larger set of mineral dust-exposed lung tissues to investigate specific histologic features of PMF and other dust-related occupational diseases.

Characterizing Lung Particulates Using Quantitative Microscopy in Coal Miners With Severe Pneumoconiosis.

CONTEXT.­: Current approaches for characterizing retained lung dust using pathologists' qualitative assessment or scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) have limitations. OBJECTIVE.­: To explore polarized light microscopy coupled with image-processing software, termed quantitative microscopy-particulate matter (QM-PM), as a tool to characterize in situ dust in lung tissue of US coal miners with progressive massive fibrosis. DESIGN.­: We developed a standardized protocol using microscopy images to characterize the in situ burden of birefringent crystalline silica/silicate particles (mineral density) and carbonaceous particles (pigment fraction). Mineral density and pigment fraction were compared with pathologists' qualitative assessments and SEM/EDS analyses. Particle features were compared between historical (born before 1930) and contemporary coal miners, who likely had different exposures following changes in mining technology. RESULTS.­: Lung tissue samples from 85 coal miners (62 historical and 23 contemporary) and 10 healthy controls were analyzed using QM-PM. Mineral density and pigment fraction measurements with QM-PM were comparable to consensus pathologists' scoring and SEM/EDS analyses. Contemporary miners had greater mineral density than historical miners (186 456 versus 63 727/mm3; P = .02) and controls (4542/mm3), consistent with higher amounts of silica/silicate dust. Contemporary and historical miners had similar particle sizes (median area, 1.00 versus 1.14 µm2; P = .46) and birefringence under polarized light (median grayscale brightness: 80.9 versus 87.6; P = .29). CONCLUSIONS.­: QM-PM reliably characterizes in situ silica/silicate and carbonaceous particles in a reproducible, automated, accessible, and time/cost/labor-efficient manner, and shows promise as a tool for understanding occupational lung pathology and targeting exposure controls.

Unexplained dyspnea linked to mitochondrial myopathy following military deployment to Southwest Asia and Afghanistan.

We identified a case of probable mitochondrial myopathy (MM) in a soldier with dyspnea and reduced exercise tolerance through cardiopulmonary exercise testing (CPET) following Southwest Asia (SWA) deployment. Muscle biopsy showed myopathic features. We compared demographic, occupational exposure, and clinical characteristics in symptomatic military deployers with and without probable MM diagnosed by CPET criteria. We evaluated 235 symptomatic military personnel who deployed to SWA and/or Afghanistan between 2010 and 2021. Of these, 168 underwent cycle ergometer maximal CPET with an indwelling arterial line. We defined probable MM based on five CPET criteria: arterial peak exercise lactate >12 mEq/L, anaerobic threshold (AT) ≤50%, maximum oxygen consumption (VO2max ) <95% predicted, oxygen (O2) pulse percent predicted (pp) at least 10% lower than heart rate pp, and elevated ventilatory equivalent for O2 at end exercise (VE/VO2 ≥ 40). We characterized demographics, smoking status/pack-years, spirometry, and deployment exposures, and used descriptive statistics to compare findings in those with and without probable MM. We found 9/168 (5.4%) deployers with probable MM. Compared to symptomatic deployers without probable MM, they were younger (p = 0.0025) and had lower mean BMI (p = 0.02). They had a higher mean forced expiratory volume (FEV1)pp (p = 0.02) and mean arterial oxygen partial pressure (PaO2) at maximum exercise (p = 0.0003). We found no significant differences in smoking status, deployment frequency/duration, or inhalational exposures. Our findings suggest that mitochondrial myopathy may be a cause of dyspnea and reduced exercise tolerance in a subset of previously deployed military personnel. CPET with arterial line may assist with MM diagnosis and management.

Vaccination Trends and Family-Level Characteristics Associated With Incomplete or Delayed Childhood Immunizations: The Healthy Start Study.

PURPOSE: Assess family-level factors associated with childhood immunization schedule adherence. DESIGN: Prospective cohort; Setting; The Healthy Start study enrolled 1,410 pregnant women in Denver, Colorado 2009-2014. SUBJECTS: Children with available vaccination data in medical records (0-6 years old). MEASURES: Vaccine schedule completion and compliance. ANALYSIS: Logistic regression comparing family-level factors that differ based on vaccine schedule adherence. RESULTS: Most immunizations required in Colorado for school entry were below national completion goals with 61.8% of participants (n = 532/861) completing the full vaccination series. Most participants received the first dose of individual vaccines on time (73.5% - 90.7%), but fewer received all doses on time (21.0% - 39.5%). Factors associated with not completing the vaccination series (OR [95% CI]) included: in-utero exposure to cigarette smoke (1.97 [1.41, 2.75]), single parent household (1.70 [1.21, 2.38]), children identified as non-White (Hispanic 1.40 [1.01, 1.94]; Black 1.88 [1.24, 2.85]; Other 2.17 [1.34, 3.49]), mothers not working outside the home (1.98 [1.46, 2.67]), and household income <$70,000 per year (<$40,000 1.93 [1.35, 2.75]; $40,000-$70,000 1.64 [1.09, 2.46]). Conversely, families with more educated mothers (0.47 [0.29, 0.76]) and older parents (0.97 [0.94, 0.99]) were significantly more likely to complete the series. CONCLUSIONS: These findings may help identify groups at risk of immunization schedule non-adherence and may be used to target education/advocacy campaigns to reduce hesitancy and increase access in these populations.