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Protein biomarkers are associated with mortality in cardiovascular disease, but their effect on predicting respiratory and all-cause mortality is not clear. We tested whether a protein risk score (protRS) can improve prediction of all-cause mortality over clinical risk factors in smokers. We utilized smoking-enriched (COPDGene, LSC, SPIROMICS) and general population-based (MESA) cohorts with SomaScan proteomic and mortality data. We split COPDGene into training and testing sets (50:50) and developed a protRS based on respiratory mortality effect size and parsimony. We tested multivariable associations of the protRS with all-cause, respiratory, and cardiovascular mortality, and performed meta-analysis, area-under-the-curve (AUC), and network analyses. We included 2232 participants. In COPDGene, a penalized regression-based protRS was most highly associated with respiratory mortality (OR 9.2) and parsimonious (15 proteins). This protRS was associated with all-cause mortality (random effects HR 1.79 [95% CI 1.31-2.43]). Adding the protRS to clinical covariates improved all-cause mortality prediction in COPDGene (AUC 0.87 vs 0.82) and SPIROMICS (0.74 vs 0.6), but not in LSC and MESA. Protein-protein interaction network analyses implicate cytokine signaling, innate immune responses, and extracellular matrix turnover. A blood-based protein risk score predicts all-cause and respiratory mortality, identifies potential drivers of mortality, and demonstrates heterogeneity in effects amongst cohorts.

BACKGROUND: The potential health benefits of exposure to vegetation, or greenness, are well documented, but there are few nationwide studies in Brazil, a country facing challenges related to land-use planning, deforestation, and environmental health risks. OBJECTIVES: In this study, we investigated the association between greenness and hospitalizations for cardiorespiratory diseases in Brazil. METHODS: We accessed hospital admissions data from 967,771 postal codes (a total of 26,724,624 admissions) covering Brazil for the period between 2008 and 2018. We used Normalized Difference Vegetation Index (NDVI) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) to measure greenness at the postal-code level. First, we applied a quasi-Poisson regression model to estimate the association between greenness and hospitalizations for circulatory and respiratory diseases, adjusted for air pollution, weather variables, and area-level socioeconomic status. We stratified the analyzes by sex, age group, health outcome, and Brazilian regions. In the second stage, we performed a meta-analysis to estimate pooled effects across the Brazilian regions. RESULTS: The national meta-analysis for the whole population, incorporating both urban and nonurban areas, showed that higher levels of greenness were associated with a lower risk of hospitalizations for circulatory diseases. An interquartile range (IQR=0.18) increase in average NDVI was associated with a 17% (95% confidence interval: 8%, 27%) lower risk of cardiovascular admissions. In contrast, there was no association found between greenness and respiratory admissions. When specifically examining urban areas, the results remained consistent with the overall findings. However, the analyses of nonurban areas revealed divergent results, suggesting that higher levels of greenness in rural regions are associated with a lower risk of hospital admissions for both circulatory and respiratory diseases. DISCUSSION: The findings emphasize the importance of prioritizing the preservation and creation of green spaces in urban areas as a means of promoting cardiovascular health in Brazil. https://doi.org/10.1289/EHP13442.

BACKGROUND: The greatest burden of chronic respiratory disease is in low- and middle-income countries, with recent population-based studies reporting substantial levels of obstructive and restrictive lung function.OBJECTIVE: To characterise the common chronic respiratory diseases encountered in hospital outpatient clinics in three African countries.METHODS This was a cross-sectional study of consecutive adult patients with chronic respiratory symptoms (>8 weeks) attending hospital outpatient departments in Ethiopia, Kenya and Sudan. Patients were assessed using a respiratory questionnaire, spirometry and chest radiography. The diagnoses of the reviewing clinicians were ascertained.RESULT: A total of 519 patients (209 Kenya, 170 Ethiopia, 140 Sudan) participated; the mean age was 45.2 years (SD 16.2); 53% were women, 83% had never smoked. Reviewing clinicians considered that 36% (95% CI 32-40) of patients had asthma, 25% (95% CI 21-29) had chronic bronchitis, 8% (95% CI 6-11) chronic obstructive pulmonary disease (COPD), 5% (95% CI 4-8) bronchiectasis and 4% (95% CI 3-6) post-TB lung disease. Spirometry consistent with COPD was present in 35% (95% CI 30-39). Restriction was evident in 38% (95% CI 33-43). There was evidence of sub-optimal diagnosis of asthma and COPD.CONCLUSION: In Ethiopia, Kenya and Sudan, asthma, COPD and chronic bronchitis account for the majority of diagnoses in non-TB patients with chronic respiratory symptoms. The suboptimal diagnosis of these conditions will require the widespread use of spirometry.

The prenatal and perinatal environments can have profound effects on the development of chronic inflammatory diseases. However, mechanistic insight into how the early-life microenvironment can impact upon development of the lung and immune system and consequent initiation and progression of respiratory diseases is still emerging. Recent studies investigating the developmental origins of lung diseases have started to delineate the effects of early-life changes in the lung, environmental exposures and immune maturation on the development of childhood and adult lung diseases. While the influencing factors have been described and studied in mostly animal models, it remains challenging to pinpoint exactly which factors and at which time point are detrimental in lung development leading to respiratory disease later in life. To advance our understanding of early origins of chronic lung disease and to allow for proper dissemination and application of this knowledge, we propose four major focus areas: 1) policy and education; 2) clinical assessment; 3) basic and translational research; and 4) infrastructure and tools, and discuss future directions for advancement. This review is a follow-up of the discussions at the European Respiratory Society Research Seminar "Early origins of lung disease: towards an interdisciplinary approach" (Lisbon, Portugal, November 2019).

Little is known about the incidence of late effects following non-Hodgkin lymphoma (NHL) among adolescent and young adult (AYA, 15-39 years) survivors. Using data from the California Cancer Registry linked to hospital discharge, we estimated the cumulative incidence of late effects at 10 years among AYAs diagnosed with NHL during 1996-2012, who survived ≥2 years. Cox proportional-hazards models were used to investigate the influence of sociodemographic and clinical factors on the occurrence of late effects. Of 4392 HIV-uninfected patients, the highest incident diseases were: endocrine (18·5%), cardiovascular (11·7%), and respiratory (5·0%), followed by secondary primary malignancy (SPM, 2·6%), renal and neurologic (2·2%), liver/pancreatic (2·0%), and avascular necrosis (1·2%). Among the 425 HIV-infected survivors, incidence was higher for all late effects, especially over threefold increased risk of SPM, compared to HIV-uninfected patients (8·1% vs. 2·6%). In multivariable models for HIV-uninfected patients, public or no health insurance (vs. private), residence in lower socioeconomic neighbourhoods (vs. higher), and receipt of a haematopoietic stem cell transplant were associated with a greater risk of most late effects. Our findings of substantial incidence of late effects among NHL AYA survivors emphasise the need for longterm follow-up and appropriate survivorship care to reduce morbidity and mortality in this vulnerable population.

Acute respiratory infections cause mortality in young children. We assessed the effects of water, sanitation, hygiene (WASH) and nutritional interventions on childhood ARI. Geographic clusters of pregnant women from rural Bangladesh were randomly assigned to receive 1) chlorinated drinking water and safe storage (W); 2) upgraded sanitation (S); 3) handwashing promotion (H); 4) combined water, sanitation, and handwashing (WSH); 5) nutrition intervention including lipid-based nutrient supplements; 6) combined WSH plus nutrition (WSHN); or 7) no intervention (control). Masking of participants was not possible. Acute respiratory illness was defined as caregiver-reported persistent cough, panting, wheezing, or difficulty breathing in the past 7 days among index children, those born to enrolled women. We assessed outcomes at 12 and 24 months of intervention using intention to treat. Compared with children in the control group (ARI prevalence, P: 8.9%), caregivers of index children reported significantly lower ARI in the water (P: 6.3%, prevalence ratio (PR): 0.71; 95% CI: 0.53, 0.96), sanitation (P: 6.4%, PR: 0.75, 95% CI: 0.58, 0.96), handwashing (P: 6.4%, PR: 0.68, 95% CI: 0.50, 0.93), and the combined WSH+N arms (P: 5.9%, PR: 0.67, 95% CI: 0.50, 0.90). Those in the nutrition (P: 7.4%, PR: 0.84, 95% CI: 0.63, 1.10) or the WSH arm (P: 8.9%, PR: 0.99, 95% CI: 0.76, 1.28) reported similar ARI prevalence compared with control children. Single targeted water, sanitation, and hygiene interventions reduced reported respiratory illness in young children. There was no apparent respiratory health benefit from combining WASH interventions.

BackgroundIdiopathic inflammatory airway disease (IAD) in cats often is described as asthmatic (eosinophilic) or bronchitic (neutrophilic), but this designation requires collection of airway fluid and it fails to consider cats with mixed airway inflammation.ObjectiveTo identify clinical features that would differentiate inflammatory disease types.AnimalsForty-nine cats with nonspecific airway inflammation identified by bronchoscopic bronchoalveolar lavage (BAL) between 2011 and 2018 were evaluated.MethodsThis is a retrospective study. Cats were categorized by BAL differential cytology as having eosinophilic (eosinophils >20% with neutrophils 50%), mixed (eosinophils 20%-50% and neutrophils >14% or discordant inflammation from 2 BAL sites), or neutrophilic (neutrophils >14% and eosinophils

RationaleThere are no population-based studies from sub-Saharan Africa describing longitudinal lung function in adults.ObjectivesTo explore the lung function trajectories and their determinants, including the effects of air pollution exposures and the cleaner-burning biomass-fuelled cookstove intervention of the Cooking and Pneumonia Study (CAPS), in adults living in rural Malawi.MethodsWe assessed respiratory symptoms and exposures, spirometry and measured 48-hour personal exposure to fine particulate matter (PM2.5) and carbon monoxide (CO), on three occasions over 3 years. Longitudinal data were analysed using mixed-effects modelling by maximum likelihood estimation.Measurements and main resultsWe recruited 1481 adults, mean (SD) age 43.8 (17.8) years, including 523 participants from CAPS households (271 intervention; 252 controls), and collected multiple spirometry and air pollution measurements for 654 (44%) and 929 (63%), respectively. Compared with Global Lung Function Initiative African-American reference ranges, mean (SD) FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) z-scores were -0.38 (1.14) and -0.19 (1.09). FEV1 and FVC were determined by age, sex, height, previous TB and body mass index, with FEV1 declining by 30.9 mL/year (95% CI: 21.6 to 40.1) and FVC by 38.3 mL/year (95% CI: 28.5 to 48.1). There was decreased exposure to PM2.5 in those with access to a cookstove but no effect on lung function.ConclusionsWe did not observe accelerated lung function decline in this cohort of Malawian adults, compared with that reported in healthy, non-smoking populations from high-income countries; this suggests that the lung function deficits we measured in adulthood may have origins in early life.

Early detection of zoonotic diseases allows for the implementation of early response measures, reducing loss of human life and economic disruption. We implemented a surveillance system in hospitals in Bangladesh to screen acutely ill hospitalized patients with severe respiratory infection and meningoencephalitis for zoonotic exposures. Patients were screened for the risk of zoonotic exposures with five questions covering vocational exposures, sick domestic animal and wild animal contact, and date palm sap consumption in the three weeks preceding illness onset. Patients giving at least one positive response were considered a potential zoonotic exposure. From September 2013 to March 2017, a total of 11 429 hospitalized patients across 14 participating hospitals were screened for exposures. Overall, 2% of patients reported a potential zoonotic exposure in the three-week period prior to becoming ill. Sixteen per cent of hospitalized patients with reported exposures died. After routine surveillance diagnostic testing, 88% of patients admitted to the hospital after a potential zoonotic exposure did not have a laboratory diagnosed aetiology for their illness. Hospital-based surveillance systems such as the Bangladeshi example presented here could play an important future role in the early detection of zoonotic spillover diseases. This article is part of the theme issue Dynamic and integrative approaches to understanding pathogen spillover.

ObjectiveTo examine the moderating role of restrictive parenting on the relation of socioeconomic status (SES) to febrile illnesses (FIs) and upper respiratory illnesses (URIs) among ethnic minority and non-minority children.MethodsChildren from diverse ethnic backgrounds (Caucasian, African American, Asian, Latino, other, or multiethnic) were followed across the course of the kindergarten year. Parents reported on SES and parenting. A nurse completed 13 physical exams per child over the year to assess FIs and URIs.ResultsDuring the school year, 28% of children (n = 199, 56% ethnic minority) exhibited one or more FIs (range, 0-6) and 90% exhibited one or more URIs (range, 0-10). No main or moderating effects of SES or restrictive parenting on FIs or URIs were found among Caucasian children; however, among ethnic minority children, the relation of SES to FIs was conditional upon restrictive parenting (β = .66; P = .02), as the fewest FIs were found for lower SES minority children whose parents reported more restrictive practices. Additionally, among minority children, more restrictive parenting was marginally associated with fewer URIs (β = -.21; P = .05).ConclusionsUnexpectedly, among minority children the fewest illnesses occurred among lower SES children whose parents endorsed more restrictive parenting. This may be due to unique appraisals of this rearing style among minority children in lower SES environments and its potential to influence immune functioning. Results suggest variability in the effects of parenting on offspring health and support context-specific evaluations of parenting in efforts to ameliorate early health disparities.

Background: Medical comorbidity may influence treatment initiation and engagement for alcohol and other drug (AOD) use disorders. We examined the association between medical comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) treatment initiation and engagement measures.Methods: We used electronic health record and insurance claims data from 7 US health care systems to identify patients with AOD use disorders between October 1, 2014, and August 15, 2015 (N = 86,565). Among patients identified with AOD use disorders in outpatient and emergency department (ED) settings, we examined how Charlson/Deyo comorbidity index scores and medical complications of AOD use were associated with treatment initiation. Among those who initiated treatment in inpatient and outpatient/ED settings, we also examined how comorbidity and AOD use-related medical complications were associated with treatment engagement. Analyses were conducted using generalized estimating equation logistic regression modeling.Results: Among patients identified as having an AOD diagnosis in outpatient and ED settings (n = 69,965), Charlson/Deyo comorbidity index scores of 2 or more were independently associated with reduced likelihood of initiation (risk ratio [RR] = 0.80, 95% confidence interval [CI] = 0.74, 0.86; reference score = 0), whereas prior-year diagnoses of cirrhosis (RR = 1.25, 95% CI = 1.12, 1.35) and pancreatic disease (RR = 1.34, 95% CI = 1.15, 1.56) were associated with greater likelihood of initiation. Among those who were identified in outpatient/ED settings and initiated, higher comorbidity scores were associated with lower likelihood of engagement (score 1: RR = 0.85, 95% CI = 0.76, 0.94; score 2+: RR = 0.61, 95% CI = 0.53, 0.71).Conclusion: Medical comorbidity was associated with lower likelihood of initiating or engaging in AOD treatment, but cirrhosis and pancreatic disease were associated with greater likelihood of initiation. Interventions to improve AOD treatment initiation and engagement for patients with comorbidities are needed, such as integrating medical and AOD treatment.

BackgroundBronchoalveolar lavage (BAL) fluid cytology and culture are used to characterize respiratory diseases in dogs. Little is known about disorders associated with increased numbers of lymphocytes in BAL fluid.ObjectiveTo evaluate duration of clinical signs and detection of specific respiratory diagnoses in dogs with BAL lymphocytosis.AnimalsOne-hundred four client-owned dogs evaluated for respiratory signs.MethodsMedical records of dogs that had >300 cells/μL and >20% lymphocytes on a differential cell count of BAL fluid between January 1, 2006, and January 1, 2016, were reviewed retrospectively. Cases were evaluated for the duration of clinical signs and respiratory diagnoses, including aspiration injury, infectious or inflammatory respiratory disease, and airway collapse.ResultsDogs ranged in age from 0.5 to 16 years (median, 7.9 years) and had a median body weight of 11.4 kg (range, 2.0-42.7 kg). Eosinophilic lung disease was documented in 13 of 104 dogs (Group 1) and airway neutrophilia associated with infectious or inflammatory disease was found in 59 of 104 dogs (Group 2). Lymphocytosis alone in BAL fluid was described in 32 dogs (Group 3). Duration of cough did not differ among groups, but airway collapse was significantly more common in dogs with solitary lymphocytosis than in those with other types of inflammation.Conclusions and clinical importanceLymphocytosis in BAL fluid is common in dogs and, in many cases, likely represents a common response to airway injury, independent of the type or duration of insult. It is unknown whether airway collapse leads to lymphocytosis or if the inflammatory process causes airway collapse.

RationaleNoncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults.ObjectivesWe set out to explore the prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi.MethodsWe performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS [Cooking and Pneumonia Study]) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter

BackgroundGastroesophageal reflux and microaspiration (MA) of gastric juice are associated with various human respiratory diseases but not in dogs.ObjectiveTo detect the presence of bile acids in bronchoalveolar lavage fluid (BALF) of dogs with various respiratory diseases.AnimalsTwenty-seven West Highland White Terriers (WHWTs) with canine idiopathic pulmonary fibrosis (CIPF), 11 dogs with bacterial pneumonia (BP), 13 with chronic bronchitis (CB), 9 with eosinophilic bronchopneumopathy (EBP), 19 with laryngeal dysfunction (LD), 8 Irish Wolfhounds (IWHs) with previous BPs, 13 healthy WHWTs, all privately owned dogs, and 6 healthy research colony Beagles METHODS: Prospective cross-sectional observational study with convenience sampling of dogs. Bile acids were measured by mass spectrometry in BALF samples. Total bile acid (TBA) concentration was calculated as a sum of 17 different bile acids.ResultsConcentrations of TBA were above the limit of quantification in 78% of CIPF, 45% of BP, 62% of CB, 44% of EBP, 68% of LD, and 13% of IWH dogs. In healthy dogs, bile acids were detected less commonly in Beagles (0/6) than in healthy WHWTs (10/13). Concentrations of TBA were significantly higher in CIPF (median 0.013 μM, range not quantifiable [n.q.]-0.14 μM, P

Water, sanitation, and handwashing interventions may confer spillover effects on intervention recipients' neighbors by interrupting pathogen transmission. We measured geographically local spillovers in the Water Quality, Sanitation, and Handwashing (WASH) Benefits Study, a cluster-randomized trial in rural Bangladesh, by comparing outcomes among neighbors of intervention versus those of control participants. Geographically defined clusters were randomly allocated to a compound-level intervention (i.e., chlorinated drinking water, upgraded sanitation, and handwashing promotion) or control arm. From January 2015 to August 2015, in 180 clusters, we enrolled 1,799 neighboring children who were age matched to trial participants who would have been eligible for the study had they been conceived slightly earlier or later. After 28 months of intervention, we quantified fecal indicator bacteria in toy rinse and drinking water samples and measured soil-transmitted helminth infections and caregiver-reported diarrhea and respiratory illness. Neighbors' characteristics were balanced across arms. Detectable Escherichia coli prevalence in tubewell samples was lower for intervention participants' neighbors than control participants' (prevalence ratio = 0.83; 95% confidence interval: 0.73, 0.95). Fecal indicator bacteria prevalence did not differ between arms for other environmental samples. Prevalence was similar in neighbors of intervention participants versus those of control participants for soil-transmitted helminth infection, diarrhea, and respiratory illness. A compound-level water, sanitation, and handwashing intervention reduced neighbors' tubewell water contamination but did not affect neighboring children's health.

BackgroundImported horses that have undergone recent long distance transport might represent a serious risk for spreading infectious respiratory pathogens into populations of horses.ObjectiveTo investigate the frequency of shedding of respiratory pathogens in recently imported horses.AnimalsAll imported horses with signed owner consent (n = 167) entering a USDA quarantine for contagious equine metritis from October 2014 to June 2016 were enrolled in the study.MethodsProspective observational study. Enrolled horses had a physical examination performed and nasal secretions collected at the time of entry and subsequently if any horse developed signs of respiratory disease during quarantine. Samples were assayed for equine influenza virus (EIV), equine herpesvirus type-1, -2, -4, and -5 (EHV-1, -2, -4, -5), equine rhinitis virus A (ERAV), and B (ERBV) and Streptococcus equi subspecies equi (S. equi) using quantitative PCR (qPCR).ResultsEquine herpesviruses were detected by qPCR in 52% of the study horses including EHV-2 (28.7%), EHV-5 (40.7%), EHV-1 (1.2%), and EHV-4 (3.0%). Clinical signs were not correlated with being qPCR-positive for EHV-4, EHV-2, or EHV-5. None of the samples were qPCR-positive for EIV, ERAV, ERBV, and S. equi. The qPCR assay failed quality control for RNA viruses in 25% (46/167) of samples.Conclusions and clinical importanceClinical signs of respiratory disease were poorly correlated with qPCR positive status for EHV-2, -4, and -5. The importance of γ-herpesviruses (EHV-2 and 5) in respiratory disease is poorly understood. Equine herpesvirus type-1 or 4 (EHV-1 or EHV-4) were detected in 4.2% of horses, which could have serious consequences if shedding animals entered a population of susceptible horses. Biosecurity measures are important when introducing recently imported horses into resident US populations of horses.

In a town located in a desert area of Northern Chile, gold and copper open-pit mining is carried out involving explosive processes. These processes are associated with increased dust exposure, which might affect children's respiratory health. Therefore, we aimed to quantify the causal attributable risk of living close to the mines on asthma or allergic rhinoconjunctivitis risk burden in children. Data on the prevalence of respiratory diseases and potential confounders were available from a cross-sectional survey carried out in 2009 among 288 (response: 69 % ) children living in the community. The proximity of the children's home addresses to the local gold and copper mine was calculated using geographical positioning systems. We applied targeted maximum likelihood estimation to obtain the causal attributable risk (CAR) for asthma, rhinoconjunctivitis and both outcomes combined. Children living more than the first quartile away from the mines were used as the unexposed group. Based on the estimated CAR, a hypothetical intervention in which all children lived at least one quartile away from the copper mine would decrease the risk of rhinoconjunctivitis by 4.7 percentage points (CAR: - 4.7 ; 95 % confidence interval ( 95 % CI): - 8.4 ; - 0.11 ); and 4.2 percentage points (CAR: - 4.2 ; 95 % CI: - 7.9 ; - 0.05 ) for both outcomes combined. Overall, our results suggest that a hypothetical intervention intended to increase the distance between the place of residence of the highest exposed children would reduce the prevalence of respiratory disease in the community by around four percentage points. This approach could help local policymakers in the development of efficient public health strategies.

In a town located in a desert area of Northern Chile, gold and copper open-pit mining is carried out involving explosive processes. These processes are associated with increased dust exposure, which might affect children's respiratory health. Therefore, we aimed to quantify the causal attributable risk of living close to the mines on asthma or allergic rhinoconjunctivitis risk burden in children. Data on the prevalence of respiratory diseases and potential confounders were available from a cross-sectional survey carried out in 2009 among 288 (response: 69 % ) children living in the community. The proximity of the children's home addresses to the local gold and copper mine was calculated using geographical positioning systems. We applied targeted maximum likelihood estimation to obtain the causal attributable risk (CAR) for asthma, rhinoconjunctivitis and both outcomes combined. Children living more than the first quartile away from the mines were used as the unexposed group. Based on the estimated CAR, a hypothetical intervention in which all children lived at least one quartile away from the copper mine would decrease the risk of rhinoconjunctivitis by 4.7 percentage points (CAR: - 4.7 ; 95 % confidence interval ( 95 % CI): - 8.4 ; - 0.11 ); and 4.2 percentage points (CAR: - 4.2 ; 95 % CI: - 7.9 ; - 0.05 ) for both outcomes combined. Overall, our results suggest that a hypothetical intervention intended to increase the distance between the place of residence of the highest exposed children would reduce the prevalence of respiratory disease in the community by around four percentage points. This approach could help local policymakers in the development of efficient public health strategies.

BackgroundLittle is known about the long-term health effects of ambient ultrafine particles (

BackgroundElemental sulfur, "the oldest of all pesticides," is the most heavily used agricultural pesticide in California and Europe. Sulfur is considered relatively safe and is used in both conventional and organic farming systems. Adverse respiratory effects have been reported in applicators and animals, but the effect on residential populations, and especially on children living in proximity to fields treated with elemental sulfur, is not known.ObjectivesWe evaluated associations between residential proximity to elemental sulfur applications and respiratory symptoms and spirometry of children living in an agricultural community.MethodsParticipants were enrolled in the CHAMACOS longitudinal birth cohort. We collected respiratory symptomatology for 347 children at 7 y of age and measured spirometry on a subset of 279. Of these, estimations of proximity to sulfur application and relevant covariate data were available for 237 and 205 children for whom we had symptomatology information and FEV1 measurements, respectively. Data from the California Pesticide Use Reporting System were used to estimate the amount of elemental sulfur applied within 0.5, 1, and 3km of a child's residence during the week, month, and 12 mo prior to pulmonary evaluation. Regression models controlled for maternal smoking during pregnancy; season of birth; PM2.5 (particulate matter ≤2.5mm in aerodynamic diameter); breast feeding duration; child's sex, age, and height; technician; and other covariates.ResultsAdverse associations with respiratory outcomes were found for sulfur applications within 0.5- and 1-km radii. Specifically, asthma medication usage and respiratory symptoms increased [OR=3.51; 95% confidence interval (CI): 1.50, 8.23, p=0.004; OR=2.09; 95% CI: 1.27, 3.46, p=0.004, respectively] and FEV1 decreased (β=−0.143; 95% CI: −0.248, −0.039, p=0.008) per 10-fold increase in the estimated amount of sulfur used within 1 km of child residence during the year prior to pulmonary evaluation.ConclusionsThis study suggests that elemental sulfur use, allowed in both organic and conventional farming, in close proximity to residential areas, may adversely affect children's respiratory health. https://doi.org/10.1289/EHP528.

IMPORTANCE: Cough is a critical human reflex and also among the most frequent symptoms in medicine. Despite the prevalence of disordered cough in laryngeal pathologies, comprehensive and quantitative evaluation of cough in these patients is lacking. OBJECTIVE: Herein we seek to establish normative values for cough aerodynamics to provide a population standard for reference in future studies. DESIGN, SETTING, AND PARTICIPANTS: Healthy subjects were recruited from an outpatient clinic to perform voluntary cough. Subjects were instructed on the technique for maximal voluntary cough production with measurements recorded on pneumotachograph. Fifty-two subjects were studied, including 29 women and 23 men with a mean age of 51.6 and 52.3 years, respectively. Main Outcomes and Measures: Cough peak airflow, peak pressure, and expiratory rise time. Results were stratified by age, gender, and height. RESULTS: Peak airflow demonstrated significant differences across age, gender, and height, with flow increasing according to increasing height. Peak cough pressure also increased with height and was significantly greater in males versus females. Expiratory rise time, the time from glottal opening to peak airflow, did not vary with age or height but was statistically significantly longer in women. CONCLUSIONS: Cough aerodynamics can be readily measured objectively in the outpatient setting. Expiratory rise time, peak flow, and peak pressure are important aspects of each cough epoch. Normative data provided herein can be used for future studies of patients with laryngotracheal disorders, and these cough parameters may prove to be simple, accessible, and repeatable outcome measures.

A pilot project was conducted to examine the health status and possible adverse health effects associated with seawater exposure (microbial water-quality indicators and phytoplankton abundance and their toxins) of surfers in Monterey Bay, Central California coastal waters. Forty-eight surfers enrolled in the study and completed an initial health background survey and weekly health surveys online using Survey Monkey. Descriptive statistics and generalized estimating equation, a regression technique, were used to identify longitudinal and correlated results. The surfers were predominately Caucasian, male, and physically active. They surfed approximately 4 h a week. Their average age was 34 years. The data indicated that the surfers were generally "healthy," with a low prevalence of diabetes, high cholesterol, and hypertension. Their most common health problems were allergies and asthma. During the study, 10% of the surfers reported gastrointestinal symptoms and 29% reported upper respiratory symptoms. This study suggests surfers were significantly more likely to report upper respiratory symptoms when they had a history of allergies, housemates with upper respiratory symptoms, and/or a history of previous adverse health symptoms while surfing during a "red tide" (an event often associated with the presence of phytoplankton toxins). Additionally, female surfers reported upper respiratory symptoms more than males.

A pilot project was conducted to examine the health status and possible adverse health effects associated with seawater exposure (microbial water-quality indicators and phytoplankton abundance and their toxins) of surfers in Monterey Bay, Central California coastal waters. Forty-eight surfers enrolled in the study and completed an initial health background survey and weekly health surveys online using Survey Monkey. Descriptive statistics and generalized estimating equation, a regression technique, were used to identify longitudinal and correlated results. The surfers were predominately Caucasian, male, and physically active. They surfed approximately 4 h a week. Their average age was 34 years. The data indicated that the surfers were generally "healthy," with a low prevalence of diabetes, high cholesterol, and hypertension. Their most common health problems were allergies and asthma. During the study, 10% of the surfers reported gastrointestinal symptoms and 29% reported upper respiratory symptoms. This study suggests surfers were significantly more likely to report upper respiratory symptoms when they had a history of allergies, housemates with upper respiratory symptoms, and/or a history of previous adverse health symptoms while surfing during a "red tide" (an event often associated with the presence of phytoplankton toxins). Additionally, female surfers reported upper respiratory symptoms more than males.

BackgroundOutdoor fine particulate matter (≤ 2.5 μm; PM2.5) has been identified as a global health threat, but the number of large U.S. prospective cohort studies with individual participant data remains limited, especially at lower recent exposures.ObjectivesWe aimed to test the relationship between long-term exposure PM2.5 and death risk from all nonaccidental causes, cardiovascular (CVD), and respiratory diseases in 517,041 men and women enrolled in the National Institutes of Health-AARP cohort.MethodsIndividual participant data were linked with residence PM2.5 exposure estimates across the continental United States for a 2000-2009 follow-up period when matching census tract-level PM2.5 exposure data were available. Participants enrolled ranged from 50 to 71 years of age, residing in six U.S. states and two cities. Cox proportional hazard models yielded hazard ratio (HR) estimates per 10 μg/m3 of PM2.5 exposure.ResultsPM2.5 exposure was significantly associated with total mortality (HR = 1.03; 95% CI: 1.00, 1.05) and CVD mortality (HR = 1.10; 95% CI: 1.05, 1.15), but the association with respiratory mortality was not statistically significant (HR = 1.05; 95% CI: 0.98, 1.13). A significant association was found with respiratory mortality only among never smokers (HR = 1.27; 95% CI: 1.03, 1.56). Associations with 10-μg/m3 PM2.5 exposures in yearly participant residential annual mean, or in metropolitan area-wide mean, were consistent with baseline exposure model results. Associations with PM2.5 were similar when adjusted for ozone exposures. Analyses of California residents alone also yielded statistically significant PM2.5 mortality HRs for total and CVD mortality.ConclusionsLong-term exposure to PM2.5 air pollution was associated with an increased risk of total and CVD mortality, providing an independent test of the PM2.5-mortality relationship in a new large U.S. prospective cohort experiencing lower post-2000 PM2.5 exposure levels.CitationThurston GD, Ahn J, Cromar KR, Shao Y, Reynolds HR, Jerrett M, Lim CC, Shanley R, Park Y, Hayes RB. 2016. Ambient particulate matter air pollution exposure and mortality in the NIH-AARP Diet and Health cohort. Environ Health Perspect 124:484-490; http://dx.doi.org/10.1289/ehp.1509676.

The independent and joint effects of within- and between-city contrasts in air pollution on mortality have been investigated rarely. To examine the differential effects of between- versus within-city contrasts in pollution exposure, we used both ambient measurements and land use regression models to assess associations with mortality and exposure to nitrogen dioxide (NO2) among ~735,600 adults in 10 of the largest Canadian cities. We estimated exposure contrasts partitioned into within- and between-city contrasts, and the sum of these as overall exposures, for every year from 1984 to 2006. Residential histories allowed us to follow subjects annually during the study period. We calculated hazard ratios (HRs) adjusted for many personal and contextual variables. In fully-adjusted, random-effects models, we found positive associations between overall NO2 exposures and mortality from non-accidental causes (HR per 5 p.p.b.: 1.05; 95% confidence interval (CI): 1.03-1.07), cardiovascular disease (HR per 5 p.p.b.: 1.04; 95% CI: 1.01-1.06), ischaemic heart disease (HR per 5 p.p.b.: 1.05; 95% CI: 1.02-1.08) and respiratory disease (HR per 5 p.p.b.: 1.04; 95% CI: 0.99-1.08), but not from cerebrovascular disease (HR per 5 p.p.b.: 1.01; 95% CI: 0.96-1.06). We found that most of these associations were determined by within-city contrasts, as opposed to by between-city contrasts in NO2. Our results suggest that variation in NO2 concentrations within a city may represent a more toxic mixture of pollution than variation between cities.

BackgroundSeveral lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment.MethodsA pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled.ResultsBaseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia.ConclusionsIn these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms, testing for non-infectious respiratory diseases may be underutilized in the HIV-infected population.

BackgroundCleaning workers are regularly exposed to cleaning products containing hazardous chemicals. This study investigated acute symptoms associated with chemical exposures among cleaning workers and their safe work practices.MethodsThis cross-sectional study included 183 cleaning workers employed in an academic medical center and affiliated health sciences campuses in Northern California. Data on respiratory, eye, skin, neurological, and gastrointestinal symptoms and occupational factors were collected by in-person interviews or self-administered questionnaires.ResultsChemical-related symptoms (several times monthly or more often) were more common among workers who performed patient area cleaning (44%) than hospital custodians (36%) or campus custodians (28%). After controlling for age, sex, and job title, symptoms were associated with exposure to carpet cleaners (OR = 2.98, 95% CI 1.28-6.92), spray products (OR = 2.82, 95% CI 1.16-6.82), solvents (OR = 2.71, 95% CI 1.20-6.15), and multi-purpose cleaners (OR = 2.58, 935% CI 1.13-6.92). Except for gloves, regular use of personal protective equipment was infrequent.ConclusionsStudy findings suggest a need for additional interventions such as use of less toxic products to reduce health risks among cleaning workers.

RationaleInvasive pulmonary aspergillosis has been increasingly reported in nonneutropenic patients, including those with underlying respiratory diseases.ObjectivesWe compared the diagnostic performances of galactomannan, 1,3-β-D-glucan, and Aspergillus-specific lateral-flow device tests with that of conventional culture by using bronchoalveolar lavage fluid samples from patients with underlying respiratory diseases.MethodsWe analyzed 268 bronchoalveolar lavage samples from 221 patients with underlying respiratory diseases (and without hematologic malignancy or previous solid organ transplantation) that were collected for routine microbiological workup between February 2012 and May 2014 at the University Hospital of Graz, Austria. Invasive pulmonary aspergillosis was defined according to European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria modified for patients with respiratory diseases.Measurements and main resultsThirty-one patients (14%) had probable or proven, 25 possible, and the remaining 165 patients no invasive pulmonary aspergillosis. Probable/proven aspergillosis was associated with a significantly higher (P = 0.034) 30-day mortality rate of 32%. Sensitivities, specificities, and diagnostic odd ratios differed markedly between galactomannan (cut-off 0.5: optical density index, 0.97, 0.81, 124.4; cut-off 1.0: 0.97, 0.93, 422.1; cut-off 3.0: 0.61, 0.99, 109.8), β-D-glucan (cut-off 80 pg/ml: 0.90, 0.42, 6.57; cut-off 200 pg/ml: 0.70, 0.61, 3.7), lateral-flow device tests (0.77, 0.92, 41.8), and mycological culture (0.29, 0.97, 14).ConclusionsProbable or proven invasive pulmonary aspergillosis was diagnosed in 14% of our study population and associated with significantly higher 30-day mortality rates. Although the performance of β-D-glucan was limited by low specificity and that of mycological culture by low sensitivity, the Aspergillus lateral-flow device seems to be a promising alternative to galactomannan testing, which remains the diagnostic gold standard for aspergillosis. Clinical trial registered with www.clinicaltrials.gov (NCT 02058316).

BackgroundThe risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown.MethodsEight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score.ResultsAt enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD.ConclusionsAlthough acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

A third of the world's population uses solid fuel derived from plant material (biomass) or coal for cooking, heating, or lighting. These fuels are smoky, often used in an open fire or simple stove with incomplete combustion, and result in a large amount of household air pollution when smoke is poorly vented. Air pollution is the biggest environmental cause of death worldwide, with household air pollution accounting for about 3·5-4 million deaths every year. Women and children living in severe poverty have the greatest exposures to household air pollution. In this Commission, we review evidence for the association between household air pollution and respiratory infections, respiratory tract cancers, and chronic lung diseases. Respiratory infections (comprising both upper and lower respiratory tract infections with viruses, bacteria, and mycobacteria) have all been associated with exposure to household air pollution. Respiratory tract cancers, including both nasopharyngeal cancer and lung cancer, are strongly associated with pollution from coal burning and further data are needed about other solid fuels. Chronic lung diseases, including chronic obstructive pulmonary disease and bronchiectasis in women, are associated with solid fuel use for cooking, and the damaging effects of exposure to household air pollution in early life on lung development are yet to be fully described. We also review appropriate ways to measure exposure to household air pollution, as well as study design issues and potential effective interventions to prevent these disease burdens. Measurement of household air pollution needs individual, rather than fixed in place, monitoring because exposure varies by age, gender, location, and household role. Women and children are particularly susceptible to the toxic effects of pollution and are exposed to the highest concentrations. Interventions should target these high-risk groups and be of sufficient quality to make the air clean. To make clean energy available to all people is the long-term goal, with an intermediate solution being to make available energy that is clean enough to have a health impact.

BackgroundGuidelines and performance measures recommend obtaining blood cultures in selected patients hospitalized with community-acquired pneumonia (CAP). Due to inherent diagnostic uncertainty, there may be spillover effects of these recommendations on other conditions that resemble pneumonia.MethodsUsing data from the 2002 to 2010 National Hospital Ambulatory Medical Care Survey, a nationally representative sample of emergency department (ED) visits in the United States, we analyzed trends in obtaining cultures in patients hospitalized with respiratory symptoms due to a nonpneumonia illness using linear regression.ResultsThe most common primary admission diagnoses for these visits included heart failure (16%), chronic obstructive pulmonary disease (13%), and chest pain (12%). The proportion of cultures collected in the ED during these visits increased from 10% (95% confidence interval [CI]: 7%-14%) in 2002 to 20% (95% CI: 16%-26%) in 2010 (P

OBJECTIVE: Chronic lung disease has been associated with greater impairment in self-reported physical function in HIV-infected patients. We sought to study this association using objective measures of physical function and pulmonary function. DESIGN: Baseline data from the Examinations of HIV Associated Lung Emphysema study, a multicenter observational cohort of HIV-infected and uninfected veterans. METHODS: We assessed the association between clinical, laboratory, and pulmonary function measures with 6-minute walk test (6-MWT). Multivariable linear regression models were generated to identify factors associated with 6-MWT performance. RESULTS: Three hundred forty participants completed 6-MWT (mean age 55 years), with 68% blacks, 94% men, and 62% current smokers. Overall, 180 (53%) were HIV-infected and 63 (19%) had spirometry-defined chronic obstructive pulmonary disease. In a multivariable model, age, current smoking, and obesity (body mass index > 30) were independently associated with lower 6-MWT performance, but HIV infection was not; there was a significant interaction between HIV and chronic cough, such that distance walked among HIV-infected participants with chronic cough was 51.76 m less (P = 0.04) compared with those without cough or HIV. Among HIV-infected participants, the forced expiratory volume in 1 second (FEV1, percent predicted), to a greater extent than total lung capacity or diffusing capacity, attenuated the association with chronic cough; decreased FEV1 was independently associated with lower 6-MWT performance in those with HIV. CONCLUSIONS: Older age, current smoking, and airflow limitation were important determinants of 6-MWT performance in the HIV-infected participants. These findings suggest that potential interventions to improve physical function may include early management of respiratory symptoms and airflow limitation.

BackgroundChronic exposure to traffic-related air pollution (TRAP) may contribute to premature mortality, but few studies to date have addressed this topic.ObjectivesIn this study we assessed the association between TRAP and mortality in Toronto, Ontario, Canada.MethodsWe collected nitrogen dioxide samples over two seasons using duplicate two-sided Ogawa passive diffusion samplers at 143 locations across Toronto. We calibrated land use regressions to predict NO2 exposure on a fine scale within Toronto. We used interpolations to predict levels of particulate matter with aerodynamic diameter < or = 2.5 microm (PM(2.5)) and ozone levels. We assigned predicted pollution exposures to 2,360 subjects from a respiratory clinic, and abstracted health data on these subjects from medical billings, lung function tests, and diagnoses by pulmonologists. We tracked mortality between 1992 and 2002. We used standard and multilevel Cox proportional hazard models to test associations between air pollution and mortality.ResultsAfter controlling for age, sex, lung function, obesity, smoking, and neighborhood deprivation, we observed a 17% increase in all-cause mortality and a 40% increase in circulatory mortality from an exposure contrast across the interquartile range of 4 ppb NO2. We observed no significant associations with other pollutants.ConclusionsExposure to TRAP was significantly associated with increased all-cause and circulatory mortality in this cohort. A high prevalence of cardiopulmonary disease in the cohort probably limits inference of the findings to populations with a substantial proportion of susceptible individuals.

ObjectiveTo estimate the tobacco-attributable costs of diseases separately for smoked and smokeless tobacco use in India.MethodsThe prevalence-based attributable-risk approach was used to estimate the economic cost of tobacco using healthcare expenditure data from the National Sample Survey, a nationally representative household sample survey conducted in India in 2004. Four major categories of tobacco-related disease-tuberculosis, respiratory diseases, cardiovascular diseases and neoplasms-were considered.ResultsDirect medical costs of treating tobacco related diseases in India amounted to $907 million for smoked tobacco and $285 million for smokeless tobacco. The indirect morbidity costs of tobacco use, which includes the cost of caregivers and value of work loss due to illness, amounted to $398 million for smoked tobacco and $104 million for smokeless tobacco. The total economic cost of tobacco use amounted to $1.7 billion. Tuberculosis accounted for 18% of tobacco-related costs ($311 million) in India. Of the total cost of tobacco, 88% was attributed to men.ConclusionsThe cost of tobacco use was many times more than the expenditures on tobacco control by the government of India and about 16% more than the total tax revenue from tobacco. The tobacco-attributable cost of tuberculosis was three times higher than the expenditure on tuberculosis control in India. The economic costs estimated here do not include the costs of premature mortality from tobacco use, which is known to comprise roughly 50% to 80% of the total economic cost of tobacco in many countries.

BackgroundC57BL/6 mice have attenuated allergic airway hyperresponsiveness (AHR) when compared with Balb/c mice but the underlying mechanisms remain unclear. SP-D, an innate immune molecule with potent immunosuppressive activities may have an important modulatory role in the allergic airway response and the consequent physiological changes. We hypothesized that an elevated SP-D production is associated with the impaired ability of C57BL/6 mice to develop allergic AHR.MethodsSP-D mRNA and protein expression was investigated during development of allergic airway changes in a model of Aspergillus fumigatus (Af)-induced allergic inflammation. To study whether strain dependency of allergic AHR is associated with different levels of SP-D in the lung, Balb/c and C57BL/6 mice were compared.ResultsSensitization and exposure to Af induced significant airway inflammation in both mouse strains in comparison with naïve controls. AHR to acetylcholine however was significantly attenuated in C57BL/6 mice in spite of increased eosinophilia and serum IgE when compared with Balb/c mice (p < 0.05). Af challenge of sensitized C57BL/6 mice induced a markedly increased SP-D protein expression in the SA surfactant fraction (1,894 +/- 170% of naïve controls) that was 1.5 fold greater than the increase in Balb/c mice (1,234 +/- 121% p < 0.01). These changes were selective since levels of the hydrophobic SP-B and SP-C and the hydrophilic SP-A were significantly decreased following sensitization and challenge with Af in both strains. Further, sensitized and exposed C57BL/6 mice had significantly lower IL-4 and IL-5 in the BAL fluid than that of Balb/c mice (p < 0.05).ConclusionsThese results suggest that enhanced SP-D production in the lung of C57BL/6 mice may contribute to an attenuated AHR in response to allergic airway sensitization. SP-D may act by inhibiting synthesis of Th2 cytokines.