BACKGROUND: Earlier antiretroviral therapy (ART) may decrease progression to advanced HIV disease (AHD) with CD4 <200 cells/mm3 or clinical sequelae. We assessed factors associated with AHD among people living with HIV (PLHIV) before and during the "test and treat" era. SETTING: The African Cohort Study (AFRICOS) prospectively enrolls adults with and without HIV from 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. METHODS: Enrollment evaluations included clinical history, physical examination, and laboratory testing. Generalized estimating equations were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CI) for factors associated with CD4 <200 at study visits. RESULTS: From 2013-2021, 3059 PLHIV with available CD4 at enrollment were included; median age was 38 years [interquartile range: 30-46] and 41.3% were men. From 2013 to 2021, the prevalence of CD4 <200 decreased from 10.5% to 3.1% while the percentage on ART increased from 76.6% to 100% (p <0.001). Factors associated with higher odds of CD4 <200 were male sex (aOR 1.56 [CI 1.29-1.89]), being 30-39 years (1.42 [1.11-1.82]) or older (compared to <30), World Health Organization stage 2 disease (1.91 [1.48-2.49]) or higher (compared to stage 1), and HIV diagnosis eras 2013-2015 (2.19 [1.42-3.37]) or later (compared to <2006). Compared to ART naïve, unsuppressed participants, being viral load suppressed on ART, regardless of ART duration, was associated with lower odds of CD4 <200 (<6 months on ART: 0.45 [0.34-0.58]). CONCLUSION: With ART scale-up, AHD has declined. Efforts targeting timely initiation of suppressive ART may further reduce AHD risk.

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.

INTRODUCTION: Despite antiretroviral therapy (ART) scale-up among people living with HIV (PLHIV), those with advanced HIV disease (AHD) (defined in adults as CD4 count <200 cells/mm(3) or clinical stage 3 or 4), remain at high risk of death from opportunistic infections. The shift from routine baseline CD4 testing towards viral load testing in conjunction with "Test and Treat" has limited AHD identification. METHODS: We used official estimates and existing epidemiological data to project deaths from tuberculosis (TB) and cryptococcal meningitis (CM) among PLHIV-initiating ART with CD4 <200 cells/mm(3) , in the absence of select World Health Organization recommended diagnostic or therapeutic protocols for patients with AHD. We modelled the reduction in deaths, based on the performance of screening/diagnostic testing and the coverage and efficacy of treatment/preventive therapies for TB and CM. We compared projected TB and CM deaths in the first year of ART from 2019 to 2024, with and without CD4 testing. The analysis was performed for nine countries: South Africa, Kenya, Lesotho, Mozambique, Nigeria, Uganda, Zambia, Zimbabwe and the Democratic Republic of Congo. RESULTS: The effect of CD4 testing comes through increased identification of AHD and consequent eligibility for protocols for AHD prevention, diagnosis and management; algorithms for CD4 testing avert between 31% and 38% of deaths from TB and CM in the first year of ART. The number of CD4 tests required per death averted varies widely by country from approximately 101 for South Africa to 917 for Kenya. CONCLUSIONS: This analysis supports retaining baseline CD4 testing to avert deaths from TB and CM, the two most deadly opportunistic infections among patients with AHD. However, national programmes will need to weigh the cost of increasing CD4 access against other HIV-related priorities and allocate resources accordingly.

BACKGROUND: Determining the prevalence of pre-treatment HIV drug resistance (PDR) is important to assess the effectiveness of first-line therapies. To determine PDR prevalence in Papua New Guinea (PNG), we conducted a nationally representative survey. METHODS: We used a two-stage cluster sampling method to recruit HIV treatment initiators with and without prior exposure to antiretroviral therapies (ART) in selected clinics. Dried blood spots were collected and tested for PDR. RESULTS: A total of 315 sequences were available for analysis. The overall PDR prevalence rate was 18.4% (95% CI 13.8-24.3%). The prevalence of PDR to non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) was 17.8% (95% CI 13.6-23.0%) and of PDR to nucleoside reverse transcriptase inhibitors (NRTIs) was 6.3% (95% CI 1.6-17.1%). The PDR prevalence rate among people reinitiating ART was 42.4% (95% CI 29.1-56.4%). CONCLUSIONS: PNG has a high PDR prevalence rate, especially to NNRTI-based first-line therapies. Our findings suggest that removing NNRTIs as part of first-line treatment is warranted and will lead to improving viral suppression rates in PNG.

The World Health Organization (WHO) currently supports baseline CD4 testing for people living with human immunodeficiency virus (PLHIV) who are initiating or re-initiating antiretroviral therapy (ART) and cryptococcal antigen (CrAg) screening for persons with a CD4 count less than 100 cells/mL and up to 200 cells/mL within an advanced-disease package of care [1, 2]. Some PLHIV taking ART will experience viral load (VL) nonsuppression (VL ≥1000 copies/mL) and may not have CD4 results available to inform CrAg screening. Therefore, we read with interest the study of VL-directed CrAg screening to prevent cryptococcal meningitis (CM) and mortality by Mpoza et al [3]. While we applaud the authors for investigating this important and multifaceted topic, we disagree with several study assumptions and interpretations.

CONTEXT: Local agencies across the United States have identified public health isolation sites for individuals with coronavirus disease 2019 (COVID-19) who are not able to isolate in residence. PROGRAM: We describe logistics of establishing and operating isolation and noncongregate hotels for COVID-19 mitigation and use the isolation hotel as an opportunity to understand COVID-19 symptom evolution among people experiencing homelessness (PEH). IMPLEMENTATION: Multiple agencies in Atlanta, Georgia, established an isolation hotel for PEH with COVID-19 and noncongregate hotel for PEH without COVID-19 but at risk of severe illness. PEH were referred to the isolation hotel through proactive, community-based testing and hospital-based testing. Daily symptoms were recorded prospectively. Disposition location was recorded for all clients. EVALUATION: During April 10 to September 1, 2020, 181 isolation hotel clients (77 community referrals; 104 hospital referrals) were admitted a median 3 days after testing. Overall, 32% of community referrals and 7% of hospital referrals became symptomatic after testing positive; 83% of isolation hotel clients reported symptoms at some point; 93% completed isolation. Among 302 noncongregate hotel clients, median stay was 18 weeks; 61% were discharged to permanent housing or had a permanent housing discharge plan. DISCUSSION: Overall, a high proportion of PEH completed isolation at the hotel, suggesting a high level of acceptability. Many PEH with COVID-19 diagnosed in the community developed symptoms after testing, indicating that proactive, community-based testing can facilitate early isolation. Noncongregate hotels can be a useful COVID-19 community mitigation strategy by bridging PEH at risk of severe illness to permanent housing.

BACKGROUND: We investigated patients with potential SARS-CoV-2 reinfection in the United States during May-July 2020. METHODS: We conducted case finding for patients with potential SARS-CoV-2 reinfection through the Emerging Infections Network. Cases reported were screened for laboratory and clinical findings of potential reinfection followed by requests for medical records and laboratory specimens. Available medical records were abstracted to characterize patient demographics, comorbidities, clinical course, and laboratory test results. Submitted specimens underwent further testing, including RT-PCR, viral culture, whole genome sequencing, subgenomic RNA PCR, and testing for anti-SARS-CoV-2 total antibody. RESULTS: Among 73 potential reinfection patients with available records, 30 patients had recurrent COVID-19 symptoms explained by alternative diagnoses with concurrent SARS-CoV-2 positive RT-PCR, 24 patients remained asymptomatic after recovery but had recurrent or persistent RT-PCR, and 19 patients had recurrent COVID-19 symptoms with concurrent SARS-CoV-2 positive RT-PCR but no alternative diagnoses. These 19 patients had symptom recurrence a median of 57 days after initial symptom onset (interquartile range: 47 - 76). Six of these patients had paired specimens available for further testing, but none had laboratory findings confirming reinfections. Testing of an additional three patients with recurrent symptoms and alternative diagnoses also did not confirm reinfection. CONCLUSIONS: We did not confirm SARS-CoV-2 reinfection within 90 days of the initial infection based on the clinical and laboratory characteristics of cases in this investigation. Our findings support current CDC guidance around quarantine and testing for patients who have recovered from COVID-19.

BACKGROUND: In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies. METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7-May 6, 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire. RESULTS: Overall, 2,875 individuals at 24 shelters and nine unsheltered outreach events underwent SARS-CoV-2 testing and 2,860 (99.5%) had conclusive test results. SARS-CoV-2 prevalence was 2.1% (36/1,684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases compared with RT-PCR. Prevalence by shelter ranged 0%-27.6%. Repeat testing 3-4 weeks later at four shelters documented decreased SARS-CoV-2 prevalence (0%-3.9%). Nine of 24 shelters completed shelter assessments and implemented IPC measures as part of the COVID-19 response. CONCLUSIONS: PEH living in shelters experienced higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for identification and isolation of COVID-19 cases and is an important strategy to interrupt SARS-CoV-2 transmission.

INTRODUCTION: The US President's Emergency Plan for AIDS Relief (PEPFAR) was launched to increase access to antiretroviral treatment (ART) among people living with HIV (PLHIV) and to prevent new HIV infections globally. As new infections have decreased in many PEPFAR-supported countries, PEPFAR is increasingly focusing on understanding and decreasing mortality among PLHIV, specifically by addressing advanced HIV disease (AHD) and its attendant opportunistic infections (OIs). Several developments in identifying AHD, in preventing, diagnosing, and treating selected OIs, and in PEPFAR's support for mortality surveillance make this an opportune moment for PEPFAR to address HIV-related mortality. DISCUSSION: AHD upon diagnosis or re-engagement in HIV care is not uncommon, and it substantially increases risk of death from OIs. The World Health Organization provides evidence-based guidelines for a package of interventions for preventing, diagnosing, and treating common OIs, including tuberculosis (TB), cryptococcal meningitis, and severe bacterial infections. PEPFAR facilitates implementation of these guidelines. To identify PLHIV with low CD4, PEPFAR plans to support expanded access to CD4 testing, including a point-of-care assay that differentiates CD4 cell count as a binary of greater than or less than 200 cells/microL. To prevent AHD-related mortality, PEPFAR supports rapid ART initiation with integrase inhibitor-based regimens and implementation and documentation of TB preventive treatment. To diagnose selected OIs, PEPFAR is implementing urine lateral flow lipoarabinomannan use to identify TB among PLHIV who have a CD4 cell count < 200 cells/microL. To treat selected OIs, PEPFAR has focused on improving patient-centered care in TB/HIV co-infection services and scaling up implementation of new drug regimens for cryptococcal meningitis. To better understand mortality, PEPFAR has introduced an indicator, TX_ML, to routinely and systematically categorize outcomes, including deaths, among PLHIV on ART. CONCLUSIONS: PEPFAR is increasing its efforts to identify AHD; to prevent, diagnose, and treat OIs; and to track mortality in its programs. These ongoing efforts, done in collaboration with other stakeholders, seek to decrease mortality among PLHIV.

BACKGROUND: As Zimbabwe approaches epidemic control of HIV, programs now prioritize viral load over CD4 monitoring, making it difficult to identify persons living with HIV (PLHIV) suffering from advanced disease (AD). We present an analysis of cross-sectional ZIMPHIA data, highlighting PLHIV with AD and concurrent viral load suppression (VLS). METHODS: ZIMPHIA collected blood specimens for HIV testing from 22,501 consenting adults (ages 15 years and older); 3,466 PLHIV had CD4 and VL results. Household HIV testing used the national serial algorithm, and those testing positive then received point-of-care CD4 enumeration with subsequent VL testing. We used logistic regression analysis to explore factors associated with concurrent AD and VLS (<1000 copies/mL). All analyses were weighted to account for complex survey design. RESULTS: Of the 3,466 PLHIV in the survey with CD4 and VL results, 17% were found to have AD (CD4<200cells/mm3). Of all AD patients, 30% had VLS. Concurrent AD and VLS was associated with male sex (aOR 2.45 95%CI 1.61-3.72), older age (35-49 years [aOR 2.46 95%CI 1.03-5.91] and 50+ years [aOR 4.82 95%CI 2.02-11.46] vs 15-24 years), and ART duration (<6 months [aOR 0.46 95%CI 0.29-0.76] and 6-24 months [aOR 2.07 95%CI 1.35-3.17] vs more than 2 years). The relationship between sex and AD is driven by age with significant associations among men aged 25-34, (aOR 3.37 95%CI 1.35-8.41), 35-49 (aOR 5.13 95%CI 2.16-12.18), and 50+ (aOR 12.56 95%CI 4.82-32.72) versus men aged 15-24. CONCLUSIONS: The percentage of PLHIV with AD and VLS illustrates the conundrum of decreased support for CD4 monitoring, as these patients may not receive appropriate clinical services for advanced HIV disease. In high-prevalence settings such as Zimbabwe, CD4 monitoring support warrants further consideration to differentiate care appropriately for the most vulnerable PLHIV. Males may need to be prioritized, given their over-representation in this sub-population.

Importance: Few studies have investigated the association of long-term ambient ozone exposures with respiratory morbidity among individuals with a heavy smoking history. Objective: To investigate the association of historical ozone exposure with risk of chronic obstructive pulmonary disease (COPD), computed tomography (CT) scan measures of respiratory disease, patient-reported outcomes, disease severity, and exacerbations in smokers with or at risk for COPD. Design, Setting, and Participants: This multicenter cross-sectional study, conducted from November 1, 2010, to July 31, 2018, obtained data from the Air Pollution Study, an ancillary study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). Data analyzed were from participants enrolled at 7 (New York City, New York; Baltimore, Maryland; Los Angeles, California; Ann Arbor, Michigan; San Francisco, California; Salt Lake City, Utah; and Winston-Salem, North Carolina) of the 12 SPIROMICS clinical sites. Included participants had historical ozone exposure data (n = 1874), were either current or former smokers (>/=20 pack-years), were with or without COPD, and were aged 40 to 80 years at baseline. Healthy persons with a smoking history of 1 or more pack-years were excluded from the present analysis. Exposures: The 10-year mean historical ambient ozone concentration at participants' residences estimated by cohort-specific spatiotemporal modeling. Main Outcomes and Measures: Spirometry-confirmed COPD, chronic bronchitis diagnosis, CT scan measures (emphysema, air trapping, and airway wall thickness), 6-minute walk test, modified Medical Research Council (mMRC) Dyspnea Scale, COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), postbronchodilator forced expiratory volume in the first second of expiration (FEV1) % predicted, and self-report of exacerbations in the 12 months before SPIROMICS enrollment, adjusted for demographics, smoking, and job exposure. Results: A total of 1874 SPIROMICS participants were analyzed (mean [SD] age, 64.5 [8.8] years; 1479 [78.9%] white; and 1013 [54.1%] male). In adjusted analysis, a 5-ppb (parts per billion) increase in ozone concentration was associated with a greater percentage of emphysema (beta = 0.94; 95% CI, 0.25-1.64; P = .007) and percentage of air trapping (beta = 1.60; 95% CI, 0.16-3.04; P = .03); worse scores for the mMRC Dyspnea Scale (beta = 0.10; 95% CI, 0.03-0.17; P = .008), CAT (beta = 0.65; 95% CI, 0.05-1.26; P = .04), and SGRQ (beta = 1.47; 95% CI, 0.01-2.93; P = .048); lower FEV1% predicted value (beta = -2.50; 95% CI, -4.42 to -0.59; P = .01); and higher odds of any exacerbation (odds ratio [OR], 1.37; 95% CI, 1.12-1.66; P = .002) and severe exacerbation (OR, 1.37; 95% CI, 1.07-1.76; P = .01). No association was found between historical ozone exposure and chronic bronchitis, COPD, airway wall thickness, or 6-minute walk test result. Conclusions and Relevance: This study found that long-term historical ozone exposure was associated with reduced lung function, greater emphysema and air trapping on CT scan, worse patient-reported outcomes, and increased respiratory exacerbations for individuals with a history of heavy smoking. The association between ozone exposure and adverse respiratory outcomes suggests the need for continued reevaluation of ambient pollution standards that are designed to protect the most vulnerable members of the US population.

BACKGROUND: Careful monitoring for recrudescence of Wuchereria bancrofti infection is necessary in communities where mass drug administration (MDA) for the elimination of lymphatic filariasis (LF) as a public health problem has been stopped. During the post-MDA period, transmission assessment surveys (TAS) are recommended by the World Health Organization to monitor the presence of the parasite in humans. Molecular xenomonitoring (MX), a method by which parasite infection in the mosquito population is monitored, has also been proposed as a sensitive method to determine whether the parasite is still present in the human population. The aim of this study was to conduct an MX evaluation in two areas of Bangladesh, one previously endemic district that had stopped MDA (Panchagarh), and part of a non-endemic district (Gaibandha) that borders the district where transmission was most recently recorded. METHODOLOGY/PRINCIPAL FINDINGS: Mosquitoes were systematically collected from 180 trap sites per district and mosquito pools were tested for W. bancrofti using real-time PCR. A total of 23,436 intact mosquitoes, representing 31 species, were collected from the two districts, of which 10,344 (41%) were Culex quinquefasciatus, the vector of W. bancrofti in Bangladesh. All of the 594 pools of Cx. quinquefasciatus tested by real-time PCR were negative for the presence of W. bancrofti DNA. CONCLUSIONS/SIGNIFICANCE: This study suggested the absence of W. bancrofti in these districts. MX could be a sensitive tool to confirm interruption of LF transmission in areas considered at higher risk of recrudescence, particularly in countries like Bangladesh where entomological and laboratory capacity to perform MX is available.

Exposure to nitrogen dioxide (NO2), a byproduct of combustion, is associated with poor asthma control in children. We sought to determine whether gas-fueled kitchen appliance use is associated with 24-h indoor NO2 concentrations and whether these concentrations are associated with asthma morbidity in children. Children aged 5-12 years old with asthma were eligible. Mean 24-h NO2 concentration was measured in the kitchen over a four-day sampling period and gas stove use was captured in time activity diaries. The relationship between stove and oven use and daily NO2 concentration was analyzed. Longitudinal analysis assessed the effect of daily NO2 exposure on symptoms, inhaler use, and lung function. Multivariate models were adjusted for age, sex, season, and maternal education. Thirty children contributed 126 participant days of sampling. Mean indoor 24-h NO2 concentration was 58(48)ppb with a median (range) of 45(12-276)ppb. All homes had gas stoves and furnaces. Each hour of kitchen appliance use was associated with an 18ppb increase in 24-h NO2 concentration. In longitudinal multivariate analysis, each ten-fold increase in previous-day NO2 was associated with increased nighttime inhaler use (OR = 4.9, p = 0.04). There were no associations between NO2 and lung function or asthma symptoms. Higher previous-day 24-h concentration of NO2 is associated with increased nighttime inhaler use in children with asthma.

To compare diagnostic tests for onchocerciasis in a setting that has suppressed transmission, a randomized, age-stratified study was implemented in an area in Tanzania that had received 15 rounds of annual mass drug administration (MDA) with ivermectin. Study participants (N = 948) from 11 villages underwent a questionnaire, skin examination, skin snips, and blood draw. The burden of symptomatic disease was low. Ov-16 antibody rapid diagnostic test (RDT) results were positive in 38 (5.5%) participants, with 1 (0.5%), 1 (0.4%), and 2 (0.8%) in children aged 0-5, 6-10, and 11-15 years, respectively. Despite significant impact of MDA on transmission, the area would have failed to meet World Health Organization serologic criteria for stopping MDA if a full evaluation had been conducted. The specificity of the RDT, which is 97-98%, may result in the identification of a number of false positives that would exceed the current stop MDA threshold.

Introduction Population-based epidemiological evidence suggests that exposure to ambient air pollutants increases hospitalisations and mortality from chronic obstructive pulmonary disease (COPD), but less is known about the impact of exposure to air pollutants on patient-reported outcomes, morbidity and progression of COPD. Methods and analysis The Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air Pollution Study (SPIROMICS AIR) was initiated in 2013 to investigate the relation between individual-level estimates of short-term and long-term air pollution exposures, day-to-day symptom variability and disease progression in individuals with COPD. SPIROMICS AIR builds on a multicentre study of smokers with COPD, supplementing it with state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, ozone, sulfur dioxide and black carbon. In the parent study, approximately 3000 smokers with and without airflow obstruction are being followed for up to 3 years for the identification of intermediate biomarkers which predict disease progression. Subcohorts undergo daily symptom monitoring using comprehensive daily diaries. The air monitoring and modelling methods employed in SPIROMICS AIR will provide estimates of individual exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand the health effects of short-term and long-term exposures to air pollution on COPD morbidity, including exacerbation risk, patient-reported outcomes and disease progression. Ethics and dissemination The institutional review boards of all the participating institutions approved the study protocols. The results of the trial will be presented at national and international meetings and published in peer-reviewed journals. Copyright © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved.

RATIONALE: There is limited evidence of the effect of exposure to heat on COPD morbidity and the interactive effect between indoor heat and air pollution has not been established. OBJECTIVES: To determine the effect of indoor and outdoor heat exposure on COPD morbidity and to determine whether air pollution concentrations modify the effect of temperature. METHODS: Sixty-nine participants with COPD were enrolled in a longitudinal cohort study and data from the 601 participant days that occurred during the warm weather season were included in the analysis. Participants completed home environmental monitoring with measurement of temperature, relative humidity, and indoor air pollutants and simultaneous daily assessment of respiratory health with questionnaires and portable spirometry. MEASUREMENTS AND MAIN RESULTS: Participants had moderate to severe COPD and spent the majority of their time indoors. Increases in maximum indoor temperature were associated with worsening of daily Breathlessness, Cough, and Sputum Scores (BCSS) and increases in rescue inhaler use. The effect was detected on the same day and lags of 1 and 2 days. The detrimental effect of temperature on these outcomes increased with higher concentrations of indoor fine particulate matter and nitrogen dioxide (p<0.05 for interaction terms). On days that participants went outdoors, increases in maximum daily outdoor temperature were associated with increases in BCSS scores after adjusting for outdoor pollution concentrations. CONCLUSIONS: For patients with COPD that spend the majority of their time indoors, indoor heat exposure during warmer months represents a modifiable environmental exposure that may contribute to respiratory morbidity. In the context of climate change, adaptive strategies that include optimization of indoor environmental conditions are needed to protect this high risk group from adverse health effects of heat.