Widespread occurrence of pesticides in low-income housing.

BACKGROUND: Low socioeconomic status (SES) residents living in social housing, which is subsidized by government or government-funded agencies, may have higher exposures to pesticides used in indoor residences since pesticides are applied due to structural deficiencies, poor maintenance, etc. OBJECTIVE: To estimate exposure of residents in low-SES social housing built in the 1970s to legacy and current-use pesticides and to investigate factors related to exposures. METHODS: Twenty-eight particle-phase pesticides were measured in the indoor air of 46 units in seven low-income social housing, multi-unit residential buildings (MURBs) in Toronto, Canada using portable air cleaners deployed for 1 week in 2017. Pesticides analyzed were legacy and current use in the classes: organochlorines, organophosphates, pyrethroids, and strobilurins. RESULTS: At least one pesticide was detected in 89% of the units with detection frequencies (DF) for individual pesticides of up to 50%, including legacy organochlorines and current-use pesticides. Current-use pyrethroids had the highest DF and concentrations, with the highest particle-phase concentration for pyrethrin I at 32,000 pg/m3. Heptachlor, restricted for use in Canada in 1985, had the highest estimated maximum total air (particle plus gas phase) concentration of 443,000 pg/m3. Heptachlor, lindane, endosulfan I, chlorothalonil, allethrin, and permethrin (except in one study) had higher concentrations than those measured in low-income residences reported elsewhere. In addition to the intentional use of pesticides to control pests and their use in building materials and paints, tobacco smoking was significantly correlated with the concentrations of five pesticides used on tobacco crops. The distribution of pesticides with high DF in individual buildings suggested that pest eradication programs by the building management and/or pesticide use by residents were the major sources of measured pesticides. IMPACT: Low-income social housing fills a much-needed demand, but the residences are prone to pest infestation and hence pesticide use. We found exposure to at least 1 of 28 particle-phase pesticides in 89% of all 46 units tested, with the highest DF and concentrations for current-use pyrethroids and long-banned organochlorines (e.g., DDT, heptachlor) due to very high persistence indoors. Also measured were several pesticides not registered for use indoors, e.g., strobilurins used to treat building materials and pesticides used on tobacco crops. These results, which are the first Canadian data for most pesticides indoors, show widespread exposure to numerous pesticides.

Considerations from an International Regulatory and Pharmaceutical Industry (IQ MPS Affiliate) Workshop on the Standardization of Complex In Vitro Models in Drug Development.

In May 2022, there is an International Regulatory and Pharmaceutical Industry (Innovation and Quality [IQ] Microphysiological Systems [MPS] Affiliate) Workshop on the standardization of complex in vitro models (CIVMs) in drug development. This manuscript summarizes the discussions and conclusions of this joint workshop organized and executed by the IQ MPS Affiliate and the United States Food and Drug Administration (FDA). A key objective of the workshop is to facilitate discussions around opportunities and/or needs for standardization of MPS and chart potential pathways to increase model utilization in the context of regulatory decision making. Participation in the workshop included 200 attendees from the FDA, IQ MPS Affiliate, and 26 global regulatory organizations and affiliated parties representing Europe, Japan, and Canada. It is agreed that understanding global perspectives regarding the readiness of CIVM/MPS models for regulatory decision making and potential pathways to gaining acceptance is useful to align on globally. The obstacles are currently too great to develop standards for every context of use (COU). Instead, it is suggested that a more tractable approach may be to think of broadly applicable standards that can be applied regardless of COU and/or organ system. Considerations and next steps for this effort are described.

Estimating Indoor Pollutant Loss Using Mass Balances and Unsupervised Clustering to Recognize Decays.

Low-cost air quality monitors are increasingly being deployed in various indoor environments. However, data of high temporal resolution from those sensors are often summarized into a single mean value, with information about pollutant dynamics discarded. Further, low-cost sensors often suffer from limitations such as a lack of absolute accuracy and drift over time. There is a growing interest in utilizing data science and machine learning techniques to overcome those limitations and take full advantage of low-cost sensors. In this study, we developed an unsupervised machine learning model for automatically recognizing decay periods from concentration time series data and estimating pollutant loss rates. The model uses k-means and DBSCAN clustering to extract decays and then mass balance equations to estimate loss rates. Applications on data collected from various environments suggest that the CO2 loss rate was consistently lower than the PM2.5 loss rate in the same environment, while both varied spatially and temporally. Further, detailed protocols were established to select optimal model hyperparameters and filter out results with high uncertainty. Overall, this model provides a novel solution to monitoring pollutant removal rates with potentially wide applications such as evaluating filtration and ventilation and characterizing indoor emission sources.

Evaluation of fixed and adaptive concentration thresholds for particle filter systems.

Particle filtration can effectively reduce indoor concentrations of particulate matter (PM) but may incur high energy use. This study evaluates fixed and adaptive concentration thresholds to automate the operation of filtration systems. Simulated environments were derived from week-long continuous PM measurements from Dylos DC1700 (N = 104) and Alphasense OPC-N2 (N = 100) particle counters deployed in apartments in Toronto. A fixed threshold of 4.0 µg·m-3 resulted in a mean air cleaner runtime of 6.9%-21.0% depending on clean air delivery rate (CADR) and particle sensor, while providing mean concentration reductions of 67%-71% compared to operating the air cleaner constantly (runtime = 100%). In most environments, runtime could be further reduced by raising the fixed threshold while resulting in only a modest decrease in absolute and normalized mean exposure reduction. Using an adaptive threshold derived from a k-means clustering approach generally provided substantial exposure reduction while preventing high runtimes. These results were generally insensitive to cleaning power and the monitor used to measure particle concentrations. Reducing the energy usage of particle filter systems will make them a more viable and sustainable means of improving occupant health.

FDA/Arthritis Foundation osteoarthritis drug development workshop recap: Assessment of long-term benefit.

OBJECTIVE: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market. DESIGN: Summary of the one-day workshop held virtually on June 22nd, 2021. RESULTS: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit. CONCLUSIONS: Demonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.

Modeling Clothing as a Vector for Transporting Airborne Particles and Pathogens across Indoor Microenvironments.

Evidence suggests that human exposure to airborne particles and associated contaminants, including respiratory pathogens, can persist beyond a single microenvironment. By accumulating such contaminants from air, clothing may function as a transport vector and source of "secondary exposure". To investigate this function, a novel microenvironmental exposure modeling framework (ABICAM) was developed. This framework was applied to a para-occupational exposure scenario involving the deposition of viable SARS-CoV-2 in respiratory particles (0.5-20 µm) from a primary source onto clothing in a nonhealthcare setting and subsequent resuspension and secondary exposure in a car and home. Variability was assessed through Monte Carlo simulations. The total volume of infectious particles on the occupant's clothing immediately after work was 4800 µm3 (5th-95th percentiles: 870-32 000 µm3). This value was 61% (5-95%: 17-300%) of the occupant's primary inhalation exposure in the workplace while unmasked. By arrival at the occupant's home after a car commute, relatively rapid viral inactivation on cotton clothing had reduced the infectious volume on clothing by 80% (5-95%: 26-99%). Secondary inhalation exposure (after work) was low in the absence of close proximity and physical contact with contaminated clothing. In comparison, the average primary inhalation exposure in the workplace was higher by about 2-3 orders of magnitude. It remains theoretically possible that resuspension and physical contact with contaminated clothing can occasionally transmit SARS-CoV-2 between humans.

Establishing a Public Resource for Acceptable Surrogate Endpoints to Support FDA Marketing Applications.

Following a comprehensive and coordinated effort between CBER and CDER, FDA established a table of acceptable surrogate endpoints (SEs) to support drug marketing applications. The publicly accessible SE Table was first published in 2018 as a response to the 21st Century Cures Act legislation and is updated every 6 months to reflect current FDA thinking. The criteria for the table headings and content were chosen to foster succinctness and consistency, while reflecting the degree of scientific understanding for each listed SE. Prior to the publication of the SE table there was the misconception that FDA only approved drugs based on a limited number of SEs. Contrary to this viewpoint, the SE table demonstrates that FDA frequently uses SEs as they are used in over 100 disease/use and patient population combinations. This article describes the considerations and approach taken when establishing the SE table as well as a discussion of the benefits and limitations of the SE table when used by various stakeholders.

Quantitative filter forensics for semivolatile organic compounds in social housing apartments.

Residents from low-income social housing are vulnerable to adverse health effects from indoor air pollution. Particle-bound concentrations of eight phthalates and 12 polycyclic aromatic hydrocarbons (PAHs) in indoor air were measured using quantitative filter forensics with portable air cleaners deployed for three one-week periods from 2015 to 2017. The sample included 143 apartments across seven multi-unit social housing buildings in Toronto, Canada, that went through energy retrofits in 2016. Eight phthalates and six PAHs were found in more than 50% of the apartments in either of the three sampling periods. Di(2-ethylhexyl) phthalate (DEHP) and phenanthrene were the dominant phthalate and PAH, with median concentrations of 146, 143, and 130 ng/m3 and 1.51, 0.58, and 0.76 ng/m3 in the late spring of 2015, and after retrofits in late spring 2017 and winter of 2017, respectively. SVOC concentrations were generally lower after energy retrofits, with significant differences for phenanthrene, fluoranthene, and pyrene. Lower concentrations post-retrofit may be related to less overheating and less need for opening windows. Concentrations of phthalates and PAHs in this study were similar to or higher than those reported in the literature. Results suggest that the use of portable air filters is a promising method to assess concentrations of indoor particle-bound SVOCs.

Long-Term Safety and Efficacy of Tocilizumab in Early Systemic Sclerosis-Interstitial Lung Disease: Open-Label Extension of a Phase 3 Randomized Controlled Trial.

Rationale: Tocilizumab, an anti-IL-6 receptor antibody, had no statistically significant effect on skin sclerosis but preserved lung function over 48 weeks in patients with early systemic sclerosis (SSc)-associated interstitial lung disease (ILD) in a phase 3 randomized controlled trial. Objectives: Assess long-term safety and efficacy of tocilizumab. Methods: Adults with diffuse cutaneous SSc for ⩽60 months and elevated acute-phase reactants, including those with ILD, received weekly placebo or tocilizumab 162 mg subcutaneously in the 48-week, double-blind period and then open-label tocilizumab from Weeks 48 to 96 (placebo-tocilizumab; continuous-tocilizumab). Measurements and Main Results: Eighty-two of 107 patients in the placebo-tocilizumab group and 85 of 105 patients in the continuous-tocilizumab group completed 96 weeks. Mean age and disease duration were 48 years and 23 months; high-resolution computed tomography revealed ILD in 61%. Mean (95% confidence interval [CI]) change in modified Rodnan skin score from baseline to week 96 was -8.4 (-10.0 to -6.8) for placebo-tocilizumab and -9.6 (-10.9 to -8.4) for continuous-tocilizumab. Mean (95% CI) change in FVC (percent predicted) from baseline to week 96 was -3.3 (-5.1 to -1.5) for placebo-tocilizumab and -0.5 (-2.4 to 1.3) for continuous-tocilizumab among completers and, in a post hoc analysis, -4.1 (-6.7 to -1.6) and -0.6 (-3.1 to 2.0), respectively, among completers with ILD (mean [95% CI] change from Weeks 48 to 96: 0.9 [-0.8 to 2.7] and -0.4 [-2.3 to 1.5], respectively). Rates per 100 patient-years of serious adverse events from Weeks 48 to 96 were 14.8 for placebo-tocilizumab and 15.8 for continuous-tocilizumab. Conclusions: Tocilizumab preserved lung function, slowing decline in FVC, in patients with SSc, including those with ILD. Long-term safety was consistent with the known safety profile of tocilizumab. Clinical trial registered with www.clinicaltrials.gov (NCT02453256).

Indoor exposure to phthalates and polycyclic aromatic hydrocarbons (PAHs) to Canadian children: the Kingston allergy birth cohort.

BACKGROUND: Canadian children are widely exposed to phthalates and polycyclic aromatic hydrocarbons (PAHs) from indoor sources. Both sets of compounds have been implicated in allergic symptoms in children. OBJECTIVE: We characterize concentrations of eight phthalates and 12 PAHs in floor dust from the bedrooms of 79 children enrolled in the Kingston Allergy Birth Cohort (KABC). METHOD: Floor dust was collected from the bedrooms of 79 children who underwent skin prick testing for common allergens after their first birthday. Data were collected on activities, household, and building characteristics via questionnaire. RESULTS: Diisononyl phthalate (DiNP) and phenanthrene were the dominant phthalate and PAH with median concentrations of 561 µg/g and 341 ng/g, respectively. Benzyl butyl phthalate (BzBP) and chrysene had the highest variations among all tested homes, ranging from 1-95% to 1-99%, respectively. SIGNIFICANCE: Some phthalates were significantly associated with product and material use such as diethyl phthalate (DEP) with fragranced products and DiNP and DiDP with vinyl materials. Some PAHs were significantly associated with household characteristics, such as benzo[a]pyrene with smoking, and phenanthrene and fluoranthene with the presence of an attached garage. Socioeconomic status (SES) had positive and negative relationships with some concentrations and some explanatory factors. No significant increases in risk of atopy (positive skin prick test) was found as a function of phthalate or PAH dust concentrations.

The impact of emissions from an essential oil diffuser on cognitive performance.

Essential oil products are increasingly used in indoor environments and have been found to negatively contribute to indoor air quality. Moreover, the chemicals and fragrances emitted by those products may affect the central nervous system and cognitive function. This study uses a double-blind between-subject design to investigate the cognitive impact of exposure to the emissions from essential oil used in an ultrasonic diffuser. In a simulated office environment where other environmental parameters were maintained constant, 34 female and 25 male university students were randomly allocated into four essential oil exposure scenarios. The first two scenarios contrast lemon oil to pure deionized water, while the latter two focus on different levels of particulate matter differentiated by HEPA filters with non-scented grapeseed oil as the source. Cognitive function was assessed using a computer-based battery consisting of five objective tests that involve reasoning, response inhabitation, memory, risk-taking, and decision-making. Results show that exposure to essential oil emissions caused shortened reaction time at the cost of significantly worse response inhabitation control and memory sensitivity, indicating potentially more impulsive decision-making. The cognitive responses caused by scented lemon oil and non-scented grapeseed oil were similar, as was the perception of odor pleasantness and intensity.

Modeling the Removal of Water-Soluble Trace Gases from Indoor Air via Air Conditioner Condensate.

Water-soluble trace gas (WSTG) loss from indoor air via air conditioning (AC) units has been observed in several studies, but these results have been difficult to generalize. In the present study, we designed a box model that can be used to investigate and estimate WSTG removal due to partitioning to AC coil condensate. We compared the model output to measurements of a suite of organic acids cycling in an indoor environment and tested the model by varying the input AC parameters. These tests showed that WSTG loss via AC cycling is influenced by Henry's law constant of the compound in question, which is controlled by air and water temperatures and the condensate pH. Air conditioning unit specifications also impact WSTG loss through variations in the sensible heat ratio, the effective recirculation rate of air through the unit, and the timing of coil and fan operation. These findings have significant implications for indoor modeling. To accurately model the fate of indoor WSTGs, researchers must either measure or otherwise account for these unique environmental and operational characteristics.

Distribution of SARS-CoV-2 RNA signal in a home with COVID-19 positive occupants.

Although many COVID-19 patients isolate and recover at home, the dispersal of SARS-CoV-2 onto surfaces and dust within the home environment remains poorly understood. To investigate the distribution and persistence of SARS-CoV-2 in a home with COVID-19 positive occupants, samples were collected from a household with two confirmed COVID-19 cases (one adult and one child). Home surface swab and dust samples were collected two months after symptom onset (and one month after symptom resolution) in the household. The strength of the SARS-CoV-2 molecular signal in fomites varied as a function of sample location, surface material and cleaning practices. Notably, the SARS-CoV-2 RNA signal was detected at several locations throughout the household although cleaning appears to have attenuated the signal on many surfaces. Of the 24 surfaces sampled, 46% were SARS-CoV-2 positive at the time of sampling. The SARS-CoV-2 concentrations in dust recovered from floor and HVAC filter samples ranged from 104 to 105 N2 gene copies/g dust. While detection of viral RNA does not imply infectivity, this study confirms that the SARS-CoV-2 RNA signal can be detected at several locations within a COVID-19 isolation home and can persist after symptoms have resolved. In addition, the concentration of SARS-CoV-2 (normalized per unit mass of dust) recovered in home HVAC filters may prove useful for estimating SARS-CoV-2 airborne levels in homes. In this work, using the quantitative filter forensics methodology, we estimated an average integrated airborne SARS-CoV-2 concentration of 69 ± 43 copies/m3. This approach can be used to help building scientists and engineers develop best practices in homes with COVID-19 positive occupants.

Volatile organic compound and particulate matter emissions from an ultrasonic essential oil diffuser.

Ultrasonic essential oil diffusers (EODs) are a popular type of indoor scenting source. We performed a chamber study in which we measured the emissions from EODs used with lemon, lavender, eucalyptus, and grapeseed oils. Over the course of 15 min, the most abundant VOCs released from lemon, lavender, eucalyptus, and grapeseed oils were 2.6 ± 0.7 mg of d-limonene, 3.5 ± 0.4 mg of eucalyptol, 1.0 ± 0.1 mg of linalyl acetate, and 0.2 ± 0.02 mg of linalyl acetate, respectively. Each oil had a unique particulate matter (PM) emission profile in terms of size, number density, and rate. The dominant size ranges of the PM were 10-100 nm for lemon oil, 50-100 nm for lavender oil, 10-50 nm for lemon oil, and above 200 nm for grapeseed oil. PM1 emission rates of approximately 2 mg/h, 0.1 mg/h, and 3 mg/h, were observed for lemon, lavender/eucalyptus, and grapeseed oils, respectively. A fivefold increase in PM1 emission was measured when the EOD with eucalyptus oil was filled with tap water as opposed to deionized water. Modeling suggests that reasonable use cases of EODs can contribute substantially to primary and secondary PM in indoor environments, but this potential varies depending on the oil and water types used.

HVAC filtration of particles and trace metals: Airborne measurements and the evaluation of quantitative filter forensics.

Filters installed in the heating, ventilation, and air-conditioning (HVAC) systems can serve as air-cleaning and sampling devices for indoor particles. The purpose of this article is to evaluate these dual roles. An occupied home with a central HVAC system equipped with a Minimum Efficiency Reporting Value (MERV, from ASHRAE Standard 52.2) 11 filter was monitored for six weeks. Weekly airborne gravimetric and real-time sampling was performed to measure the particle size distribution and the concentration of total suspended particles (TSP), PM10, PM2.5, PM1, and 12 trace metals. The weekly system runtimes were intentionally changed to provide a wide range of weekly filtration volumes. The quantitative filter forensics (QFF) concentrations of particulate matter (PM) and trace metals were calculated using the analysis of the dust collected on the HVAC filter, the filtration volume, and filter in-situ efficiency. The results indicated that filtration was not influential to remove PM and trace metals as the concentrations during the weeks with continuous HVAC operation were not consistently lower than those during the other weeks. This suggests the dominance of other particle and trace metal source and loss mechanisms weakens the influence of filtration in this home. The QFF evaluation results indicated that the concentration of TSP and over half of the tested trace metals (e.g., Pb, Cd, Ni, V, Sb, K, and Sr) could be estimated by QFF within a factor of two when compared to airborne sampling results. PM10, PM2.5, and PM1 concentrations were significantly underestimated by QFF potentially due to the limitations of size distribution analysis by a laser diffraction particle sizer (LDPS) for the detection of <1 µm particles. Overall, while QFF was promising for TSP and some trace metals, improvement in size distribution analysis could extend the application of QFF for airborne sampling.

Quantitative filter forensics: Size distribution and particulate matter concentrations in residential buildings.

We applied filter forensics, the analysis of dust from the heating, ventilation, and air-conditioning (HVAC) filters, to measure particle size distribution in 21 residences in Toronto, Canada over a year. Four filters with different nominal efficiencies (Minimum Efficiency Reporting Value (MERV) 8-14 from ASHRAE Standard 52.2) were deployed in each residence each for three months, while the effective filtration volumes (the product of flow rate, runtime, and in-situ filter efficiency) were characterized over each filter lifetime. Using extraction and laser diffraction, we found that approximately 90% of the volumetric distributions were >10 µm and the volume median diameter (VMD) ranged from 23.4 to 75.1 µm. Using quantitative filter forensics (QFF), total suspended particle (TSP) concentrations ranged from 2.9 to 823.7 µg/m3 (median = 89.8 µg/m3 ) with a moderate correlation with the content of TSP on the filters (in terms of g) and with the TSP effective filtration volume (m3 ) indicating the importance of both filter forensics and HVAC metadata parameters to QFF concentration estimates. There was no strong correlation between PM10 or PM2.5 concentrations and hourly airborne particle number concentrations measured by low-cost sensors suggesting an evaluation of QFF is warranted, particularly for the exploration of smaller particles.

Cardiopulmonary Impact of Particulate Air Pollution in High-Risk Populations: JACC State-of-the-Art Review.

Fine particulate air pollution <2.5 µm in diameter (PM2.5) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM2.5 as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM2.5 can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention.

Personal-Level Protective Actions Against Particulate Matter Air Pollution Exposure: A Scientific Statement From the American Heart Association.

Since the publication of the last American Heart Association scientific statement on air pollution and cardiovascular disease in 2010, unequivocal evidence of the causal role of fine particulate matter air pollution (PM2.5, or particulate matter ≤2.5 µm in diameter) in cardiovascular disease has emerged. There is a compelling case to provide the public with practical personalized approaches to reduce the health effects of PM2.5. Such interventions would be applicable not only to individuals in heavily polluted countries, high-risk or susceptible individuals living in cleaner environments, and microenvironments with higher pollution exposures, but also to those traveling to locations with high levels of PM2.5. The overarching motivation for this document is to summarize the current evidence supporting personal-level strategies to prevent the adverse cardiovascular effects of PM2.5, guide the use of the most proven/viable approaches, obviate the use of ineffective measures, and avoid unwarranted interventions. The significance of this statement relates not only to the global importance of PM2.5, but also to its focus on the most tested interventions and viable approaches directed at particulate matter air pollution. The writing group sought to provide expert consensus opinions on personal-level measures recognizing the current uncertainty and limited evidence base for many interventions. In doing so, the writing group acknowledges that its intent is to assist other agencies charged with protecting public health, without minimizing the personal choice considerations of an individual who may decide to use these interventions in the face of ongoing air pollution exposure.

Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: A phase 2 trial of tocilizumab showed preliminary evidence of efficacy in systemic sclerosis. We assessed skin fibrosis and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in a phase 3 trial to investigate the safety and efficacy of tocilizumab, an anti-interleukin-6 receptor antibody, in the treatment of systemic sclerosis. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial, participants were recruited from 75 sites in 20 countries across Europe, North America, Latin America, and Japan. Adults with diffuse cutaneous systemic sclerosis for 60 months or less and a modified Rodnan skin score (mRSS) of 10-35 at screening were randomly assigned (1:1) with a voice-web-response system to receive subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks, stratified by IL-6 levels; participants and investigators were masked to treatment group. The primary endpoint was the difference in change from baseline to week 48 in mRSS. Percentage of predicted forced vital capacity (FVC% predicted) at week 48, time to treatment failure, and patient-reported and physician-reported outcomes were secondary endpoints. This trial is registered with ClinicalTrials.gov (number NCT02453256) and is closed to accrual. FINDINGS: Between Nov 20, 2015, and Feb 14, 2017, 210 individuals were randomly assigned to receive tocilizumab (n=104) or placebo (n=106). In the intention-to-treat population, least squares mean [LSM] change from baseline to week 48 in mRSS was -6·14 for tocilizumab and -4·41 for placebo (adjusted difference -1·73 [95% CI -3·78 to 0·32]; p=0·10). The shift in distribution of change from baseline in FVC% predicted at week 48 favoured tocilizumab (van Elteren nominal p=0·002 vs placebo), with a difference in LSM of 4·2 (95% CI 2·0-6·4; nominal p=0·0002), as did time to treatment failure (hazard ratio 0·63 [95% CI 0·37-1·06]; nominal p=0·08). Change in LSM from baseline to week 48 in Health Assessment Questionnaire-Disability Index and in patient-global and physician-global visual analogue scale assessments did not differ between tocilizumab and placebo. In the safety set, infections were the most common adverse events (54 [52%] of 104 participants in the tocilizumab group, 53 [50%] of 106 in the placebo group). Serious adverse events were reported in 13 participants treated with tocilizumab and 18 with placebo, primarily infections (three events, eight events) and cardiac events (two events, seven events). INTERPRETATION: The primary skin fibrosis endpoint was not met. Findings for the secondary endpoint of FVC% predicted indicate that tocilizumab might preserve lung function in people with early SSc-ILD and elevated acute-phase reactants. Safety was consistent with the known profile of tocilizumab. FUNDING: F Hoffmann-La Roche Ltd.