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Respiratory Disease

• California dominates U.S. emissions of the pesticide and potent greenhouse gas sulfuryl fluoride
  Sulfuryl fluoride (SO2F2) is a synthetic pesticide and a potent greenhouse gas that is accumulating in the global atmosphere. Rising emissions are a concern since SO2F2 has a relatively long atmospheric lifetime and a high global warming potential. The U.S. is thought to contribute substantially to global SO2F2 emissions, but there is a paucity of information on how emissions of SO2F2 are distributed across the U.S., and there is currently no inventory of SO2F2 emissions for the U.S. or individual states. Here we provide an atmospheric measurement-based estimate of U.S. SO2F2 emissions using high-precision SO2F2 measurements from the NOAA Global Greenhouse Gas Reference Network (GGGRN) and a geostatistical inverse model. We find that California has the largest SO2F2 emissions among all U.S. states, with the highest emissions from southern coastal California (Los Angeles, Orange, and San Diego counties). Outside of California, only very small and infrequent SO2F2 emissions are detected by our analysis of GGGRN data. We find that California emits 60-85% of U.S. SO2F2 emissions, at a rate of 0.26 ( ± 0.10) Gg yr−1. We estimate that emissions of SO2F2 from California are equal to 5.5–12% of global SO2F2 emissions.
  [Gaeta, D.C. et al. (2024) California dominates U.S. emissions of the pesticide and potent greenhouse gas sulfuryl fluoride, Communications Earth & Environment. Available at: https://www.nature.com/articles/s43247-024-01294-x ]
• Chlorfenapyr poisoning: mechanisms, clinical presentations, and treatment strategies
  BACKGROUND:
  Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides. Chlorfenapyr poisoning has a high mortality rate and is difficult to treat. This article aims to review the mechanisms, clinical presentations, and treatment strategies for chlorfenapyr poisoning.

  DATA RESOURCES:
  We conducted a review of the literature using PubMed, Web of Science, and SpringerLink from their beginnings to the end of October 2023. The inclusion criteria were systematic reviews, clinical guidelines, retrospective studies, and case reports on chlorfenapyr poisoning that focused on its mechanisms, clinical presentations, and treatment strategies. The references in the included studies were also examined to identify additional sources.

  RESULTS:
  We included 57 studies in this review. Chlorfenapyr can be degraded into tralopyril, which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate. High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning. Once it occurs, respiratory failure occurs immediately, ultimately leading to cardiac arrest and death. Chlorfenapyr poisoning is difficult to treat, and there is no specific antidote.

  CONCLUSION:
  Chlorfenapyr is a new pyrrole pesticide. Although it has been identified as a moderately toxic pesticide by the World Health Organization (WHO), the mortality rate of poisoned patients is extremely high. There is no specific antidote for chlorfenapyr poisoning. Therefore, based on the literature review, future efforts to explore rapid and effective detoxification methods, reconstitute intracellular oxidative phosphorylation couplings, identify early biomarkers of chlorfenapyr poisoning, and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.
  [Cheng, J. et al. (2024) Chlorfenapyr poisoning: Mechanisms, clinical presentations, and treatment strategies, World Journal of Emergency Medicine. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153369/. ]

• Exposure to agricultural pesticides and wheezing among 5–12-year-old children in the Imperial Valley, CA, USA
  Background:
  Exposure to pesticides has been linked to adverse respiratory health outcomes in children.

  Methods:
  We leveraged the Children’s Assessing Imperial Valley Respiratory Health and the Environment cohort located in the rural community of Imperial Valley near the US–Mexico border. We calculated the kilograms of total pesticides applied within 400 m of children’s residential addresses for the years 2016–2020. Estimated pesticide usage near homes was categorized into three groups (none vs. low vs. high [split at the median]). All health variables (i.e., asthma status and wheezing) were derived from a parent-reported questionnaire on respiratory health. We used generalized linear models, controlling for child sex, the language of survey, health insurance, respondents’ highest education, and exposure to environmental secondhand smoking, to calculate prevalence differences between none versus low and high exposure to agricultural pesticides.

  Results:
  Approximately 62% of the 708 children (aged 5–12 years) lived within 400 m of at least one pesticide application within 12 months prior to survey administration. Exposure to pesticides within 400 m of children’s residences was associated with 12-month prior wheeze. Those in the “high” exposure group had a prevalence of wheezing that was 10 (95% confidence interval: 2%, 17%) percentage points higher than among children not exposed to pesticide applications. Associations for high exposure to specific categories of pesticide applications, sulfur only, all pesticides except sulfur, chlorpyrifos, and glyphosate, also were observed with a higher prevalence of wheezing than among children not exposed to pesticide applications.

  Conclusions:
  We observed associations between living near pesticide applications and more wheeze symptoms among children.
  [Ornelas Van Horne, Y. et al. (2024) Exposure to agricultural pesticides and wheezing among 5–12-year-old children in the Imperial Valley, CA, USA, Environmental Epidemiology. Available at: https://journals.lww.com/environepidem/fulltext/2024/10000/exposure_to_agricultural_pesticides_and_wheezing.2.as]

• Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE)
  Background
  Pyrethroid insecticides use for indoor residual spraying (IRS) in malaria-endemic areas results in high levels of exposure to local populations. Pyrethroids may cause asthma and respiratory allergies but no prior study has investigated this question in an IRS area.
  Methods
  We measured maternal urinary concentrations of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in samples collected at delivery from 751 mothers participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. At 3.5-year and 5-year follow-up visits, caregivers of 647 and 620 children, respectively, were queried about children's respiratory allergy symptoms based on validated instruments. We applied marginal structural models for repeated outcomes to estimate associations between biomarker concentrations and asthma diagnosis as well as respiratory allergy symptoms at ages 3.5 and 5 years.
  Results
  We found that a10-fold increase in maternal urinary cis-DCCA, trans-DCCA and 3-PBA concentrations were associated with more than a doubling in the risk of doctor-diagnosed asthma (cis-DCCA: RR = 2.1, 95% CI = 1.3, 3.3; trans-DCCA: RR = 2.1, 95% CI = 1.1, 3.9; 3-PBA: RR = 2.4, 95% CI = 1.0, 5.8) and an about 80% increase in the risk of wheezing or whistling in the chest (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.0; trans-DCCA: RR = 1.7, 95% CI = 1.1, 2.6; 3-PBA: RR = 1.8, 95% CI = 1.0, 3.3) and suspected asthma (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.1; trans-DCCA: RR = 1.8, 95% CI = 1.1, 2.8). We also observed that higher concentrations of cis-DBCA and 3-PBA were related to increases in the risks of dry cough at night (RR = 3.5, 95% CI = 1.3, 9.5) and seasonal rhinoconjunctivitis (RR = 2.0, 95% CI = 1.1, 3.9), respectively.
  Conclusion
  Maternal exposure to pyrethroids may increase the risk of asthma and other respiratory allergy symptoms among preschool children from an IRS area.
  [Elsiwi, B. et al. (2024) Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), Environmental Research. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0013935123024088. ]
• Association of Lifetime Exposure to Glyphosate and Aminomethylphosphonic Acid (AMPA) with Liver Inflammation and Metabolic Syndrome at Young Adulthood: Findings from the CHAMACOS Study
   We aimed to assess whether lifetime exposure to glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), is associated with elevated liver transaminases and metabolic syndrome among young adults. We conducted a prospective cohort study (lowercase italic n equals 480n=480 mother–child dyads) and a nested case–control study (lowercase italic n equals 60n=60 cases with elevated liver transaminases and 91 controls) using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We measured glyphosate and AMPA concentrations in urine samples collected during pregnancy and at child ages 5, 14, and 18 y from cases and controls. We calculated glyphosate residue concentrations: [glyphosate plus open parenthesis 1.5 times uppercase a m p a close parenthesisglyphosate + (1.5×AMPA)]. We estimated the amount of agricultural-use glyphosate applied within a 1 kilometer1−km radius of every residence from pregnancy to age 5 y for the full cohort using California Pesticide Use Reporting data. We assessed liver transaminases and metabolic syndrome at 18 y of age. Urinary AMPA at age 5 y was associated with elevated transaminases [relative risk (RR) per two-fold increase equals 1.272−fold increase=1.27, 95% confidence interval (CI): 1.06, 1.53] and metabolic syndrome (relative risk equals 2.07RR=2.07, 95% CI: 1.38, 3.11). Urinary AMPA and glyphosate residues at age 14 y were associated with metabolic syndrome [relative risk equals 1.80RR=1.80 (95% CI: 1.10, 2.93) and relative risk equals 1.88RR=1.88 (95% CI: 1.03, 3.42), respectively]. Overall, a 2-fold increase in urinary AMPA during childhood was associated with a 14% and a 55% increased risk of elevated liver transaminases and metabolic syndrome, respectively. Living near agricultural glyphosate applications during early childhood (birth to 5 y of age) was also associated with metabolic syndrome at age 18 y in the case–control group (relative risk equals 1.53RR=1.53, 95% CI: 1.16, 2.02). Childhood exposure to glyphosate and AMPA may increase risk of liver and cardiometabolic disorders in early adulthood, which could lead to more serious diseases later in life.
  [Eskenazi, B., Gunier, R.B., Rauch, S., Kogut, K., Perito, E.R., Mendez, X., Limbach, C., Holland, N., Bradman, A., Harley, K.G. and Mills, P.J., 2023. Environmental Health Perspectives, 131(3), p.037001.]
• Increasing confidence in new approach methodologies for inhalation risk assessment with multiple end point assays using 5-day repeated exposure to 1,3-dichloropropene
  New Approach Methodologies (NAMs) are being widely used to reduce, refine, and replace, animal use in studying toxicology. For respiratory toxicology, this includes both in silico and in vitro alternatives to replace traditional in vivo inhalation studies. 1,3-Dichloropropene (1,3-DCP) is a volatile organic compound that is widely used in agriculture as a pre-planting fumigant. Short-term exposure of humans to 1,3-DCP can result in mucous membrane irritation, chest pain, headache, and dizziness. In our previous work, we exposed differentiated cells representing different parts of the respiratory epithelium to 1,3-DCP vapor, measured cytotoxicity, and did In Vitro to In Vivo Extrapolation (IVIVE). We have extended our previous study with 1,3-DCP vapors by conducting transcriptomics on acutely exposed nasal cultures and have implemented a separate 5-day repeated exposure with multiple endpoints to gain further molecular insight into our model. MucilAir™ Nasal cell culture models, representing the nasal epithelium, were exposed to six sub-cytotoxic concentrations of 1,3-DCP vapor at the air-liquid interface, and the nasal cultures were analyzed by different methodologies, including histology, transcriptomics, and glutathione (GSH) -depletion assays. We observed the dose-dependent effect of 1,3-DCP in terms of differential gene expression, change in cellular morphology from pseudostratified columnar epithelium to squamous epithelium, and depletion of GSH in MucilAir™ nasal cultures. The MucilAir™ nasal cultures were also exposed to 3 concentrations of 1,3-DCP using repeated exposure 4 h per day for 5 days and the histological analyses indicated changes in cellular morphology and a decrease in ciliated bodies and an increase in apoptotic bodies, with increasing concentrations of 1,3-DCP. Altogether, our results suggest that sub-cytotoxic exposures to 1,3-DCP lead to several molecular and cellular perturbations, providing significant insight into the mode-of-action (MoA) of 1,3-DCP using an innovative NAM model.
  [Paudel, I. et al. (2023) Increasing confidence in new approach methodologies for inhalation risk assessment with multiple end point assays using 5-day repeated exposure to 1,3-Dichloropropene, Toxicology. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0300483X23002299. ]
• Multiple Chemical Sensitivity/Idiopathic Environmental Intolerance: A Practical Approach to Diagnosis and Management
  Patients with multiple chemical sensitivity, now called idiopathic environmental intolerance, frequently present to clinical immunologists and allergists for diagnosis and treatment. Patients report a plethora of respiratory and multisystem problems attributed to a wide variety of unrelated, otherwise non-noxious, triggers. They may go to extreme, often seemingly bizarre lengths to avoid contact with everyday exposures and may become housebound, unable to work or function socially. Often beginning with exposure to odors, triggers can multiply to involve foods, clothing, medications, and even electromagnetic radiation. The condition cannot be explained by IgE-mediated or other immune processes, and clinical immunologists and allergists may feel unprepared to care for such patients. In this article, a paradigm to understand the probable mechanisms underlying this condition and a practical approach to diagnosis and management will be presented.
  [Binkley, K. (2023) Multiple chemical sensitivity/idiopathic environmental intolerance: A practical approach to diagnosis and management, The journal of allergy and clinical immunology. Available at: https://pubmed.ncbi.nlm.nih.gov/37660733/. ]
• Predicting mortality in paraquat poisoning through clinical findings, with a focus on pulmonary and cardiovascular system disorders.
  Paraquat, one of the most widely used herbicides, poses a significant risk of mortality through self-poisoning and subsequent multiple organ failure. The primary objective aimed to identify the factors associated with death in patients poisoned by paraquat. A cross-sectional retrospective review was conducted at a tertiary referral hospital over five years. Eligible patients presented with acute paraquat toxicity between 1 January 2016 and 31 December 2020. Medical records of 148 patients were reviewed. The in-hospital fatality rate was found to be 21.8%. Multivariate analysis revealed that the amount of paraquat ingested and clinical presentations, particularly pulmonary and cardiovascular system disorders, were significantly associated with mortality. Our study highlights that the amount of paraquat ingested, along with the presence of pulmonary and cardiovascular system disorders, can serve as prognostic indicators for mortality rates in cases of paraquat poisoning. These findings have important implications for physicians in predicting the prognosis and mortality of paraquat poisoning patients.
  [Tajai, P. and Kornjirakasemsan, A., 2023. Journal of Pharmaceutical Policy and Practice, 16(1), p.123.]
• Respiratory and allergic outcomes among 5-year-old children exposed to pesticides
  Background Little is known about the effects of pesticides on children’s respiratory and allergic outcomes. We evaluated associations of prenatal and current pesticide exposures with respiratory and allergic outcomes in children from the Infants’ Environmental Health Study in Costa Rica.

  Methods Among 5-year-old children (n=303), we measured prenatal and current specific gravity-corrected urinary metabolite concentrations of insecticides (chlorpyrifos, pyrethroids), fungicides (mancozeb, pyrimethanil, thiabendazole) and 2,4-D. We collected information from caregivers on respiratory (ever doctor-diagnosed asthma and lower respiratory tract infections (LRTI), wheeze and cough during last 12 months) and allergic (nasal allergies, itchy rash, ever eczema) outcomes. We fitted separate multivariable logistic regression models for high (≥75th percentile (P75)) vs low (<P75) metabolite concentrations with respiratory and allergic outcomes. We also ran models including metabolite concentrations as continuous exposure variables.

  Results Children’s respiratory outcomes were common (39% cough, 20% wheeze, 12% asthma, 5% LRTI). High current pyrethroid metabolite concentrations (∑pyrethroids) were associated with wheeze (OR=2.37, 95% CI 1.28 to 4.34), itchy rash (OR=2.74, 95% CI 1.33 to 5.60), doctor-diagnosed asthma and LRTI. High current ethylene thiourea (ETU) (specific metabolite of mancozeb) was somewhat associated with LRTI (OR=2.09, 95% CI 0.68 to 6.02). We obtained similar results when modelling ∑pyrethroids and ETU as continuous variables. We saw inconsistent or null associations for other pesticide exposures and health outcomes.

  Conclusions Current pyrethroid exposure may affect children’s respiratory and allergic health at 5 years of age. Current mancozeb exposure might contribute to LRTI. These findings are important as pyrethroids are broadly used in home environments and agriculture and mancozeb in agriculture.
  [Islam, J.Y. et al. (2023) Respiratory and allergic outcomes among 5-year-old children exposed to pesticides, Thorax. Available at: https://thorax.bmj.com/content/78/1/41.abstract. ]

• Lifetime occupational exposures and chronic obstructive pulmonary disease risk in the UK Biobank cohort
  

   Occupational exposures are important, preventable causes of COPD. We previously found an increased risk of COPD among six occupations by analysing lifetime job histories and lung function data in the population-based UK Biobank cohort. We aimed to build on these findings and elucidate the underlying potential causal agents to focus preventive strategies. We applied the ALOHA+job exposure matrix (JEM) based on the International Standard Classification of Occupations V.1988 codes, where exposure to 12 selected agents was rated as 0 (no exposure), 1 (low) or 2 (high). COPD was spirometrically defined as FEV1/FVC less than the lower limit of normal. We calculated semiquantitative cumulative exposure estimates for each agent by multiplying the duration of exposure and squared intensity. Prevalence ratio (PR) and 95% CI for COPD were estimated using robust Poisson regression adjusted for centre, sex, age, smoking and coexposure to JEM agents. Only associations confirmed among never-smokers and never-asthmatics were considered reliable. Out of 116 375 participants with complete job histories, 94 514 had acceptable/repeatable spirometry and smoking data and were included in the analysis. Pesticide exposure showed increased risk of COPD for ever exposure (PR=1.13, 95% CI 1.01 to 1.28) and high cumulative exposure (PR=1.32, 95% CI 1.12 to 1.56), with positive exposure–response trends (p trend=0.004), which were confirmed among never-smokers (p trend=0.005) and never-asthmatics (p trend=0.001). In a large population-based study, occupational exposure to pesticides was associated with risk of COPD. Focused preventive strategies for workers exposed to pesticides can prevent the associated COPD burden.

  
  [De Matteis, S., Jarvis, D., Darnton, L., Consonni, D., Kromhout, H., Hutchings, S., Sadhra, S.S., Fishwick, D., Vermeulen, R., Rushton, L. and Cullinan, P. Thorax.]
• Atrazine Inhalation Worsen Pulmonary Fibrosis Regulating the Nuclear Factor Erythroid 2-Related Factor (Nrf2) Pathways Inducing Brain Comorbidities
  Pulmonary fibrosis can be caused by genetic abnormalities, autoimmune disorders or exposure to environmental pollutants. All these causes have in common the excessive production of oxidative stress species that initiate a cascade of molecular mechanism underlying fibrosis in a variety of organs, including lungs. The chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Additionally, Bleomycin is a chemotherapeutic agent often used for different lymphoma with a seriously pulmonary complication. The most accredited hypothesis that may explain the mechanism of toxicity induced by ATR or bleomycin is exactly the production of reactive oxygen species (ROS) that leads to an unbalance in the physiological anti-oxidant system. However, until today, nobody has investigated the effect of ATR exposure during pulmonary fibrosis. Methods: Mice were subject to ATR exposure, to bleomycin injection or to both. At the end of experiment, the lungs and blood were collected. Additionally, we analyzed by different test such as open field, pole and rotarod test or other we investigated the effects of ATR or bleomycin exposure on behavior. Results: Following ATR or bleomycin induction, we found a significant increase in lung damage, fibrosis, and oxidative stress. This condition was significantly worsened when the animals injected with bleomycin were also exposed to ATR. Additionally, we observed significant motor and non-motor impairment in animals exposed to ATR. Conclusion: Our study demonstrates that ATR exposure, decrease nuclear factor-erythroid 2-related factor (Nrf2) pathways in both lung and brain.
  [D’Amico, R., Monaco, F., Fusco, R., Siracusa, R., Impellizzeri, D., Peritore, A.F., Crupi, R., Gugliandolo, E., Cuzzocrea, S., Di Paola, R. and Genovese, T. Cell. Physiol. Biochem, 55, pp.704-725.]
• Atrazine Inhalation Worsen Pulmonary Fibrosis Regulating the Nuclear Factor-Erythroid 2-Related Factor (Nrf2) Pathways Inducing Brain Comorbidities
  Pulmonary fibrosis can be caused by genetic abnormalities, autoimmune disorders or exposure to environmental pollutants. All these causes have in common the excessive production of oxidative stress species that initiate a cascade of molecular mechanism underlying fibrosis in a variety of organs, including lungs. The chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Additionally, Bleomycin is a chemotherapeutic agent often used for different lymphoma with a seriously pulmonary complication. The most accredited hypothesis that may explain the mechanism of toxicity induced by ATR or bleomycin is exactly the production of reactive oxygen species (ROS) that leads to an unbalance in the physiological anti-oxidant system. However, until today, nobody has investigated the effect of ATR exposure during pulmonary fibrosis. Mice were subject to ATR exposure, to bleomycin injection or to both. At the end of experiment, the lungs and blood were collected. Additionally, we analyzed by different test such as open field, pole and rotarod test or other we investigated the effects of ATR or bleomycin exposure on behavior. Following ATR or bleomycin induction, we found a significant increase in lung damage, fibrosis, and oxidative stress. This condition was significantly worsened when the animals injected with bleomycin were also exposed to ATR. Additionally, we observed significant motor and non-motor impairment in animals exposed to ATR. Our study demonstrates that ATR exposure, decrease nuclear factor-erythroid 2-related factor (Nrf2) pathways in both lung and brain.  
  [D'Amico, R., Monaco, F., Fusco, R., Siracusa, R., Impellizzeri, D., Peritore, A.F., Crupi, R., Gugliandolo, E., Cuzzocrea, S., Di Paola, R. and Genovese, T. Cell Physiol Biochem, 55, pp.704-725.]
• Glyphosate poisoning - a case report
  Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and the surfactant polyoxyethylene amine (POEA)- mediated cardiotoxicity. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. There is no antidote and aggressive supportive therapy is the mainstay of treatment for glyphosate poisoning. We present a 69-year-old female patient with suicidal consumption of around 500 ml of Glycel®. Initially, gastric lavage was done and intravenous fluids were given. Within two hours of presentation, the patient developed respiratory distress needing intubation, hypotension needing vasopressor support, and severe lactic acidosis. She also developed acute respiratory distress syndrome, hypokalemia, hypernatremia, and aspiration pneumonia. Our patient was critically ill with multiple poor prognostic factors, but with timely aggressive supportive management, the patient gradually recovered.
  [Kunapareddy, T. and Kalisetty, S., 2021. Journal of Postgraduate Medicine.]
• Influence of pesticides on respiratory pathology – a literature review
  Pesticides are widely employed in agriculture, and the food industry is forced to combat the pests and diseases they cause. Respiratory pathology is related to occupational exposure to pesticides. Impairment of pulmonary function was observed among people professionally exposed to pesticides. Because of the marked use of pesticides in agriculture during the last 20 years, there has been a significant increase in respiratory problems within the population, not only among people who come in direct contact with them, but even in the case of manipulators. The aim is a review of the literature of the past 10 years on the correlation between occupational exposure to pesticides and respiratory pathology. Electronic search in ‘Pub Med’ and ‘Web of Science’ was performed in September 2019 to find papers regarding the above-investigated aspects. Abstracts and full-text articles containing the targeted subject were included. Reviews and studies about the influence of pesticides on other pathologies than respiratory were excluded. After applying the inclusion and exclusion criteria, eligible full-text articles were identified. Exposure to pesticides is highly correlated with respiratory pathologies (asthma, COPD, lung cancer). Contact with these substances can occur at any time in the production, transport, preparation or application of the treatments. Numerous studies documented the association between exposure to pesticides, and therefore the increased incidence of respiratory, cardiovascular and renal diseases, as well as the aging phenomenon.
  [Tarmure, S., Alexescu, T.G., Orasan, O., Negrean, V., Sitar-Taut, A.V., Coste, S.C. and Todea, D.A., 2020. Annals of Agricultural and Environmental Medicine: AAEM, 27(2), pp.194-200.]
• Paraquat: toxicology and impacts of its ban on human health and agriculture
  Paraquat was the most successful nonselective herbicide in Korea due to its rapid herbicidal activity. However, its high mammalian toxicity, frequent self-poisoning incidents, and a lack of effective antidotes led to a paraquat ban in Korea in 2012. Therefore, this review was conducted to revisit the toxicological profile of paraquat and to investigate the impacts of the paraquat ban on human health and agriculture in Korea. A review of toxicological information reconfirmed that paraquat is highly acutely toxic to humans, and ingestion, inhalation, or dermal administration of the herbicide can cause severe clinical signs and inevitably lead to death by respiratory failure. In Korea, the paraquat ban immediately decreased the suicide rate due to pesticides (mainly paraquat) by 46.1%, resulting in a 10% decrease of the total suicide rate. However, this also led to an increase in suicide attempts with other poisons such as carbon monoxide, suggesting that suicide attempts and rates of suicide by poisoning depend on not only the toxicity of the poison but also the accessibility of the poisoning agents. In agriculture, paraquat was quickly replaced by other nonselective herbicides such as glufosinate and glyphosate. Thus, the paraquat ban did not have a significant impact on agricultural practices but influenced the nonselective herbicide market; the use of glufosinate was higher than use of glyphosate due to glufosinate’s rapid herbicidal activity, which is similar to that of paraquat. Though the paraquat ban can be considered as a national strategy to lower suicide rates, the increase in suicide attempts with other poisons suggests that multilateral efforts are required for not only keeping suicidal agents away from people but also minimizing motives for suicide.
  [Kim, J. W., & Kim, D. S. (2020). Paraquat: toxicology and impacts of its ban on human health and agriculture. Weed science, 68(3), 208-213. https://www.cambridge.org/core/journals/weed-science/article/abs/paraquat-toxicology-and-impacts-of-ban-on-human-health-and-agriculture/0E4589AEC0B5B84F5D46587C0640B235 ]
• The herbicide paraquat-induced molecular mechanisms in the development of acute lung injury and lung fibrosis
  The herbicide paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridylium dichloride) is a highly toxic organic heterocyclic herbicide that has been widely used in agricultural settings. Since its commercial introduction in the early 1960s, numerous cases of fatal PQ poisonings attributed to accidental and/or intentional ingestion of PQ concentrated formulations have been reported. The clinical manifestations of the respiratory system during the acute phase of PQ poisoning mainly include acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), followed by pulmonary fibrosis in a later phase. The focus of this review is to summarize the most recent publications related to PQ-induced lung toxicity as well as the underlying molecular mechanisms for PQ-mediated pathologic processes. Growing sets of data from in vitro and in vivo models have demonstrated the involvement of the PQ in regulating lung oxidative stress, inflammatory response, epigenetics, apoptosis, autophagy, and the progression of lung fibrosis. The article also summarizes novel therapeutic avenues based on a literature review, which can be explored as potential means to combat PQ-induced lung toxicity. Finally, we also presented clinical studies on the association of PQ exposure with the incidence of lung injury and pulmonary fibrosis.
  [Subbiah, R. and Tiwari, R.R., 2020. Critical Reviews in Toxicology, pp.1-97.]
• Pollution and children's health
  Findings
  The Lancet Commission on Pollution and Health found that pollution – air, water, soil, and chemical pollution - was responsible in 2016 for 940,000 deaths in children worldwide, two-thirds of them in children under the age of 5. Pollution is inequitably distributed, and the overwhelming majority of pollution-related deaths in children occurred in low- and middle-income countries (LMICs). Most were due to respiratory and gastrointestinal diseases caused by polluted air and water.

  Pollution is linked also to multiple non-communicable diseases (NCDs) in children including low birth weight, asthma, cancer and neurodevelopmental disorders, and these diseases are on the rise. The full impact of pollution, especially chemical pollution on the global burden of pediatric disease is not yet known, but almost certainly is undercounted because patterns of chemical exposure are not well charted and the potential toxicity of many chemical pollutants has not been characterized. The list of pediatric NCDs attributed to pollution will likely expand as the health effects of newer chemical pollutants are better defined and additional associations between pollution and disease are discovered.

  Conclusion
  Pollution prevention presents a major, largely unexploited opportunity to improve children's health and prevent NCDs, especially in LMICs. Failure to incorporate pollution prevention into NCD control programs is a major missed opportunity for disease prevention.
  [Landrigan, P. et al. (2019) ‘Pollution and children’s health’, Science of The Total Environment, 650, pp. 2389–2394. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0048969718338543?via%3Dihub. ]

• The association between 1,3-dichloropropene and asthma emergency department visits in California, USA from 2005 to 2011: a bidirectional-symmetric case crossover study
  Objective: The ever-increasing rate of pesticide use in California farmlands is of great concern due to its potential toxicity on human health. In this study, the association between short term exposure to 1,3-dichloropropene (1,3-D) and asthma emergency department (ED) visits in central and southern California from 2005 to 2011 is investigated.

  Methods: 3878 ED visits were identified from 2005 to 2011 (1064 days). Conditional logistic regression models were used to obtain the odds ratio (OR) associated with 0.01 ppb increase in 1,3-D. Potential effect modification by sex, race/ethnicity (Non-Hispanic White, Non-Hispanic Black, or Hispanic), and age (2–5, 6–18, 19–40, 41–64 or ≥ 65) are investigated.

  Results: It was found that a 0.01 ppb increase in 1,3-D at the event day is associated with 13.5% [OR = 1.135, 95% CI: 1.123, 1.149] increase in the odds of having asthma ED visits in central and southern California during October to February of 2005 to 2011. Race had a positive association between 1,3-D and asthma ED visits among Non-Hispanic Black [OR= 1.095 95% CI: 1.035, 1.155] and Hispanic [OR= 1.121 95% CI: 1.064, 1.179]; while Non-Hispanic Whites had no association. Positive association for age was found between 1,3-D and asthma ED visits among patients 2 to 5 [OR= 1.065 95% CI: 1.020, 1.133], 6 to 18 [OR= 1.142 95% CI: 1.086, 1.196], and 19 to 40 [OR= 1.023 95% CI: 1.015, 1.073] years old.

  Conclusion: These findings suggest a 0.01 ppb increase in 1,3-D concentration increases the odds of having asthma ED visits.
  [Gharibi, H. et al. (2019) The association between 1,3-dichloropropene and asthma emergency department visits in California, USA from 2005 to 2011: a bidirectional-symmetric case crossover study, Journal of Asthma. Available at: https://www.tandfonline.com/doi/abs/10.1080/02770903.2019.1590596. ]

• Impact of childhood wheezing on lung function in adulthood: A meta-analysis
  Background
  A growing body of evidence shows that childhood wheezing may lead to recurrent or persistent symptoms in adulthood, such that persistent wheezing associated with lung function deficits often have their roots in the first few years of life.

  Objectives
  We summarized information from several prospective cohort studies following children with or without wheezing into adulthood, to estimate the effect of childhood wheezing on adulthood lung function.

  Methods
  Medical literatures were searched in the Medline, PubMed, ScienceDirect, Web of Science and Embase databases up to October 31, 2016. The adulthood lung function was selected as primary outcome, and chronic obstructive pulmonary disease (COPD) prevalence was selected as secondary outcome. The meta-analysis was performed with the Stata Version 14.0. A random-effects model was applied to estimate standardized mean difference (SMD) of lung function, and relative risk (RR) of COPD.

  Results
  Six articles enrolling 1141 and 1005 children with and without wheezing, respectively. Meta-analysis showed that childhood wheezing decreased adulthood lung function as compared with no-wheezing subjects (SMD = -0.365, 95% confidence interval (CI): -0.569~-0.161, P = 0.000). Subgroup analyses indicated that childhood atopic wheezing reduced adulthood FEV1/FVC and FEV1%pred when compared with no-wheezing subjects. In addition, childhood atopic wheezing was significantly associated with COPD prevalence (RR = 5.307, 95% CI:1.033~27.271, P = 0.046).

  Conclusions
  Our meta-analysis suggests that childhood wheezing may induce ongoing declined lung function that extends into adult life, as well as an increased risk of COPD prevalence when accompanied with atopy.
  [Ma, H. et al. (2018) Impact of childhood wheezing on lung function in adulthood: A meta-analysis, PLoS ONE. Available at: https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0192390.]

• The Organophosphorus Pesticide Chlorpyrifos Induces Sex-Specific Airway Hyperreactivity in Adult Rats.
  Occupational and environmental exposures to organophosphorus pesticides (OPs) are associated with increased incidence of asthma and other pulmonary diseases. While the canonical mechanism of OP neurotoxicity is inhibition of acetylcholinesterase (AChE), it was previously reported that the OP chlorpyrifos (CPF) causes airway hyperreactivity (AHR) in guinea pigs at levels that do not inhibit lung or brain AChE. The guinea pig is considered to have inherently hyperresponsive airways, thus, cross-species validation is needed to confirm relevance to humans. Additionally, sex differences in asthma incidence have been demonstrated in the human population, but whether OP-induced AHR is sex-dependent has not been systematically studied in a preclinical model. In this study, eight-week old male and female Sprague Dawley rats were administered CPF at doses causing comparable AChE inhibition in whole lung homogenate (30 mg/kg in males, 7 mg/kg in females, sc) prior to assessing pulmonary mechanics in response to electrical stimulation of the vagus nerves at 24 h, 48 h, 72 h, 7 d or 14 d post-exposure in males, and 24 h or 7 d post-exposure in females. CPF significantly potentiated vagally-induced airway resistance and tissue elastance at 7 d post-exposure in males, and at 24 h and 7 d post-exposure in females. These effects occurred independent of significant AChE inhibition in cerebellum, blood, trachealis, or isolated airway, suggesting that AChE-independent OP-induced airway hyperreactivity is a cross-species phenomenon. These findings have significant implications for assessing the risk posed by CPF, and potentially other OPs, to human health and safety.
  [Shaffo FC, Grodzki AC, Schelegle ES, Lein PJ. 2018. Toxicol Sci. doi: 10.1093/toxsci/kfy158.]
• Elemental Sulfur Use and Associations with Pediatric Lung Function and Respiratory Symptoms in an Agricultural Community (California, USA)
  Background:
  Elemental 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.
  Objectives:
  We evaluated associations between residential proximity to elemental sulfur applications and respiratory symptoms and spirometry of children living in an agricultural community.
  Methods:
  Participants 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.
  Results:
  Adverse 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,
  [Raanan, R. et al. (2017) Elemental Sulfur Use and Associations with Pediatric Lung Function and Respiratory Symptoms in an Agricultural Community (California, USA), Environmental Health Perspectives. Available at: https://ehp.niehs.nih.gov/doi/full/10.1289/EHP528. ]
• Exposure to pesticides and the associated human health effects.
  Pesticides are used widely to control weeds and insect infestation in agricultural fields and various pests and disease carriers (e.g., mosquitoes, ticks, rats, and mice) in houses, offices, malls, and streets. As the modes of action for pesticides are not species-specific, concerns have been raised about environmental risks associated with their exposure through various routes (e.g., residues in food and drinking water). Although such hazards range from short-term (e.g., skin and eye irritation, headaches, dizziness, and nausea) to chronic impacts (e.g., cancer, asthma, and diabetes), their risks are difficult to elucidate due to the involvement of various factors (e.g., period and level of exposure, type of pesticide (regarding toxicity and persistence), and the environmental characteristics of the affected areas). There are no groups in the human population that are completely unexposed to pesticides while most diseases are multi-causal to add considerable complexity to public health assessments. Hence, development of eco-friendly pesticide alternatives (e.g., EcoSMART) and Integrated Pest Management (IPM) techniques is desirable to reduce the impacts of pesticides. This paper was hence organized to present a comprehensive review on pesticides with respect to their types, environmental distribution, routes of exposure, and health impacts.
  [Kim KH, Kabir E, Jahan SA. 2017. Sci Total Environ. 575:525-535.]
• Occupational exposure to pesticides are associated with fixed airflow obstruction in middle-age.
  Population-based studies have found evidence of a relationship between occupational exposures and Chronic Obstructive Pulmonary Disease (COPD), but these studies are limited by the use of prebronchodilator spirometry. Establishing this link using postbronchodilator is critical, because occupational exposures are a modifiable risk factor for COPD.This study investigated the associations between occupational exposures and fixed airflow obstruction using postbronchodilator spirometry. One thousand three hundred and thirty-five participants were included from 2002 to 2008 follow-up of the Tasmanian Longitudinal Health Study (TAHS). Spirometry was performed and lifetime work history calendars were used to collect occupational history. ALOHA plus Job Exposure Matrix was used to assign occupational exposure, and defined as ever exposed and cumulative exposure unit (EU)-years. Fixed airflow obstruction was defined by postbronchodilator FEV1/FVC <0.7 and the lower limit of normal (LLN). Ever exposure to biological dust (relative risk (RR)=1.58, 95% CI 1.01 to 2.48), pesticides (RR=1.74,95% CI 1.00 to 3.07) and herbicides (RR=2.09,95% CI 1.18 to 3.70) were associated with fixed airflow obstruction. Cumulative EU-years to all pesticides (RR=1.11,95% CI 1.00 to 1.25) and herbicides (RR=1.15,95% CI 1.00 to 1.32) were also associated with fixed airflow obstruction. In addition, all pesticides exposure was consistently associated with chronic bronchitis and symptoms that are consistent with airflow obstruction. Pesticides and herbicides exposures were associated with fixed airflow obstruction and chronic bronchitis. Biological dust exposure was also associated with fixed airflow obstruction in non-asthmatics. Minimising occupational exposure to these agents may help to reduce the burden of COPD.
  [Alif SM, Dharmage SC, Benke G, Dennekamp M, et al. 2017. Thorax. pii: thoraxjnl-2016-209665]
• Pesticides are Associated with Allergic and Non-Allergic Wheeze among Male Farmers
  Growing evidence suggests that pesticide use may contribute to respiratory symptoms. We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers. Using the 2005–2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by ≥ 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n = 3,939, 18%); men without wheeze were the referent. In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure–response models with up to five exposure categories, we saw evidence of an exposure–response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin. These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects.
  [Hoppin J.A., Umbach D.M., Long S., London S.J., Henneberger P.K., Blair A., Alavanja M., Beane Freeman L.E., Sandler D.P. 2017. 125:535–543; http://dx.doi.org/10.1289/EHP315]
• Environmental pollutants and child health-A review of recent concerns
  In recent years, many new studies have evaluated associations between environmental pollutants and child health. This review aims to provide a broad summary of this literature, comparing the state of epidemiological evidence for the effects of a wide range of environmental contaminants (air pollutants, heavy metals, organochlorine compounds, perfluoroalkyl substances, polybrominated diphenyl ethers, pesticides, phthalates and bisphenol A) on child health outcomes. The review addresses effects on foetal growth and prematurity, neurodevelopment, respiratory and immune health, and childhood growth and obesity. Findings of recent prospective studies and meta-analyses have corroborated previous good evidence, often at lower exposure levels, for effects on foetal growth of air pollution and polychlorinated biphenyls (PCBs), for neurotoxic effects of lead, methylmercury, PCBs and organophosphate pesticides, and for respiratory health effects of air pollution. Moderate evidence has emerged for a potential role of environmental pollutants in attention deficit hyperactivity disorder and autism (lead, PCBs, air pollution), respiratory and immune health (dichlorodiphenyldichloroethylene - DDE - and PCBs), and obesity (DDE). In addition, there is now moderate evidence that certain chemicals of relatively recent concern may be associated with adverse child health outcomes, specifically perfluorooctanoate and foetal growth, and polybrominated diphenyl ethers and neurodevelopment. For other chemicals of recent concern, such as phthalates and bisphenol A, the literature is characterised by large inconsistencies preventing strong conclusions. In conclusion, since most of the recent literature evaluates common exposures in the general population, and not particularly high exposure situations, this accumulating body of evidence suggests that the unborn and young child require more protection than is currently provided. Large, coordinated research efforts are needed to improve understanding of long-term effects of complex chemical mixtures.
  [Vrijheid M, Casas M, Gascon M, Valvi D, Nieuwenhuijsen M. 2016. Int J Hyg Environ Health. 219(4-5):331-42]
• Glyphosate pathways to modern diseases V: Amino acid analogue of glycine in diverse proteins
  Glyphosate, a synthetic amino acid and analogue of glycine, is the most widely used biocide on the planet. Its presence in food for human consumption and animal feed is ubiquitous. Epidemiological studies have revealed a strong correlation between the increasing incidence in the United States of a large number of chronic diseases and the increased use of glyphosate herbicide on corn, soy and wheat crops. Glyphosate, acting as a glycine analogue, may be mistakenly incorporated into peptides during protein synthesis. A deep search of the research literature has revealed a number of protein classes that depend on conserved glycine residues for proper function. Glycine, the smallest amino acid, has unique properties that support flexibility and the ability to anchor to the plasma membrane or the cytoskeleton. Glyphosate substitution for conserved glycines can easily explain a link with diabetes, obesity, asthma, chronic obstructive pulmonary disease (COPD), pulmonary edema, adrenal insufficiency, hypothyroidism, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, prion diseases, lupus, mitochondrial disease, nonHodgkin’s lymphoma, neural tube defects, infertility, hypertension, glaucoma, osteoporosis, fatty liver disease and kidney failure. The correlation data together with the direct biological evidence make a compelling case for glyphosate action as a glycine analogue to account for much of glyphosate’s toxicity. Glufosinate, an analogue of glutamate, likely exhibits an analogous toxicity mechanism. There is an urgent need to find an effective and economical way to grow crops without the use of glyphosate and glufosinate as herbicides.
  [Samsel, A. and Seneff, S., 2016. J Biol Phys Chem, 16(6), pp.9-46.]
• Early-life exposure to organophosphate pesticides and pediatric respiratory symptoms in the CHAMACOS cohort.
  Authors investigated the relationship between early-life exposure to OPs and respiratory outcomes.Participants included 359 mothers and children from the CHAMACOS birth cohort. Dialkyl phosphate (DAP) metabolites of OP pesticides, specifically diethyl (DE) and dimethyl (DM) phosphate metabolites, were measured in urine from mothers twice during pregnancy (mean = 13 and 26 weeks gestation) and from children five times during childhood (0.5-5 years). Mothers reported their child's respiratory symptoms at 5 and 7 years of age. Higher prenatal DAP concentrations, particularly DE, were nonsignificantly associated with respiratory symptoms in the previous 12 months at 5 or 7 years of age. This association was strongest with total DAP and DE from the second half of pregnancy. Childhood DAP, DE, and DM concentrations were associated with respiratory symptoms and exercise-induced coughing in the previous 12 months at 5 or 7 years of age. Early-life exposure to OP pesticides was associated with respiratory symptoms consistent with possible asthma in childhood.
  [Raanan R, Harley KG, Balmes JR, et al. 2015. Environ Health Perspect. 123(2):179-85.]
• Asthma associated with pesticide exposure among women in rural Western Cape of South Africa.
  Few studies have investigated asthma and pesticides among women farm workers in developing countries.
  A cross-sectional study was conducted to investigate the association between pesticides and asthma among rural women (n = 211). Outcome measurements included respiratory symptoms (European Community Respiratory Health Survey questionnaire), immunological status (Phadiatop, serum IgE to mite allergens) and lower airway inflammation (fractional exhaled nitric oxide (FeNO) levels). Exposure variables included self-reported pesticide exposure and whole blood cholinesterase (ChE). The prevalence of ocular-nasal symptoms (ONS), doctor-diagnosed asthma and current asthma was 24%, 11%, and 6% respectively. ONS was positively associated with re-entering a sprayed field. Asthma symptom score was associated with low ChE. Participants with high FeNO (>50 ppb) also had an elevated odds of having low ChE. Pesticide exposure among women farm workers is associated with increased risk of ocular nasal symptoms and an elevated asthma symptom score.
  [Ndlovu V, Dalvie MA, Jeebhay MF. 2014. Am J Ind Med. 57(12):1331-43.]
• Levels and sources of volatile organic compounds in homes of children with asthma.
  This study characterizes VOC levels in 126 homes of children with asthma in Detroit, Michigan, USA. The total target VOC concentration ranged from 14 to 2274 μg/m(3); 56 VOCs were quantified; and d-limonene, toluene, p, m-xylene, and ethyl acetate had the highest concentrations. Based on the potential for adverse health effects, priority VOCs included naphthalene, benzene, 1,4-dichlorobenzene, isopropylbenzene, ethylbenzene, styrene, chloroform, 1,2-dichloroethane, tetrachloroethene, and trichloroethylene. Concentrations varied mostly due to between-residence and seasonal variation. Identified emission sources included cigarette smoking, solvent-related emissions, renovations, household products, and pesticides. The effect of nearby traffic on indoor VOC levels was not distinguished. While concentrations in the Detroit homes were lower than levels found in other North American studies, many homes had elevated VOC levels, including compounds that are known health hazards. Thus, the identification and control of VOC sources are important and prudent, especially for vulnerable individuals. The most important sources included cigarette smoking, vehicle-related emissions, building renovation, solvents, household products, and pesticides.
  [Chin JY, Godwin C, Parker E, et al. 2014. Indoor Air. 24(4):403-15.]
• The association of respiratory symptoms and indoor housing conditions among migrant farmworkers in eastern North Carolina.
  Farm labor housing has been described as among the worst in the nation, oftentimes with poor and unsanitary indoor living conditions. The objective of this study was to evaluate the association between indoor environmental risk factors and respiratory health among migrant farmworker occupants (N = 352) living in employer-provided housing. A cross-sectional sample of adult Latino male farm laborers were administered a questionnaire to identify the prevalence of major respiratory symptoms. Self-reported and independent observations were made to evaluate environmental respiratory risk factors and indoor housing conditions, including but not limited to, the presence of cockroaches, rodents, pesticides, and visible signs of mold. Spirometry was performed to evaluate lung function using FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), and FEV1 /FVC ratio. Bivariate analysis was applied to evaluate associations between respiratory symptoms and selected indoor environmental risk factors. Findings for respiratory health included prevalence of wheeze (11.4%), coughing up phlegm (17.3%), tightness of chest (16.8%), and runny or stuffy nose (34.4%). Respiratory risks identified inside the dwellings included the use of pesticides or bug sprays for cockroaches (31.5%), rat or mouse poison (19.5%), visible signs of water damage in the bathroom (22.5%), and mold in the sleeping room (11.1%). Spirometry values were normal for most occupants, although statistically significant associations were found between mold and coughing up phlegm when not having a cold (P = .0262); presence of mold and asthma (P = .0084); pesticides used in the home and tightness of chest (P = .0001); and use of tobacco and coughing up phlegm (P = .0131). Although causal inference can be difficult to establish from a cross-sectional study, findings from this study represents suggestive evidence that indoor environmental risk factors may be contributory factors for respiratory health problems among this vulnerable workgroup population.
  [Kearney GD, Chatterjee AB, Talton J, et al. 2014. J Agromedicine. 19(4):395-405.]
• Prenatal exposure to pesticide ingredient piperonyl butoxide and childhood cough in an urban cohort.
  A previous study from the authors reports that airborne concentrations of cis-permethrin, but not trans-permethrin, measured during pregnancy in an inner city pediatric cohort was associated with cough by age 5. However, the effect of subsequent exposures to both permethrins during early childhood, and to piperonyl butoxide (PBO, a synergist for residential pyrethroid insecticides) remains to be elucidated. This study hypothesized that prenatal and age 5-6 year measures of PBO and permethrins would be associated with cough at age 5-6 years in this cohort. Further, the authors explored the associations between these pesticide measures and wheeze, asthma, seroatopy, and fractional exhaled nitric oxide (FeNO).PBO and permethrins were measured in personal air during the third trimester of pregnancy and indoor residential air at age 5-6 years (n=224). Health outcome questionnaires were administered to the mothers of 5-6 year old children. Indoor allergen specific and total immunoglobulin (Ig) E production was measured from sera collected at age 5, and FeNO was measured at 5-6 years.Noninfectious cough was reported among 14% of children at age 5-6 years. Measures of prenatal PBO, but not age 5-6 year PBO or permethrins, increased the odds of cough. No significant associations were found for other measured health outcomes.Authors conclude prenatal PBO exposure was associated with childhood cough. It is unclear whether the observed effect is due mainly to PBO itself or residential pyrethroids of which PBO is an indicator.
  [Liu B, Jung KH, Horton MK, et al. 2012. Environ Int. 48:156-61.]
• Rhinitis associated with pesticide exposure among commercial pesticide applicators in the Agricultural Health Study
  To investigate the association between current rhinitis and pesticide use, authors used data from 2245 Iowa commercial pesticide applicators in the Agricultural Health Study. 74% of commercial pesticide applicators reported at least one episode of rhinitis in the past year (current rhinitis). Five pesticides used in the past year were significantly positively associated with current rhinitis: the herbicides 2,4-D, glyphosate and petroleum oil, the insecticide diazinon and the fungicide benomyl. The association for 2,4-D and glyphosate was limited to individuals who used both in the past year (OR 1.42, 95% CI 1.14 to 1.77). Both petroleum oil and diazinon showed consistent evidence of an association with rhinitis, based on both current use and exposure–response models.
  [R E Slager, J A Poole, T D LeVan, et al. 2009. Occup Environ Med 2009 66: 718-724]
• Respiratory symptoms in children and exposure to pesticides
  A cross­sectional study was performed on children from a randomly selected sample of Lebanese public schools. Exposure to pesticides was evaluated by a standardised questionnaire and a residential exposure score, and respiratory symptoms were assessed. A chronic respiratory disease was reported in 407 (12.4%) out of 3,291 children. The baseline difference in mean age was small but statistically significant. Any exposure to pesticides, including residential, para­occupational and domestic, was associated with respiratory disease and chronic respiratory symptoms (chronic phlegm, chronic wheezing, ever wheezing), except for chronic cough.
  [Salameh, PR, I Baldi, P Brochard, et al. 2003. European Respiratory Journal 22: 507-512]
• Chemical predictors of wheeze among farmer pesticide applicators in the Agricultural Health Study.
  Using the Agricultural Health Study, a large cohort of certified pesticide applicators in Iowa and North Carolina, authors explored the association between wheeze and pesticide use in the past year. Self-administered questionnaires contained items on 40 currently used pesticides and pesticide application practices. A total of 20,468 applicators, ranging in age from 16 to 88 years, provided complete information; 19% reported wheezing in the past year. The herbicides, atrazine and alachlor, but not 2,4-D, were associated with wheeze. Atrazine had a significant dose-response trend with participants applying atrazine more than 20 days/year.These associations, though small, suggest an independent role for specific pesticides in respiratory symptoms of farmers.
  [Hoppin, JA, DM Umbach, SJ London, et al. 2002. M J Respir Crit Care Med 165: 683-689]
• Identifying and managing adverse environmental health effects: Pesticides.
  Pesticide exposure can cause many different health effects, from acute problems such as dermatitis and asthma exacerbation to chronic problems such as chronic obstructive pulmonary disease and cancer. The resulting clinical presentations are undifferentiated, and specific knowledge of the links to environmental exposures is often required for effective diagnosis. In this article we illustrate the use of the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Drugs and Diet), a history-taking tool that assists physicians in quickly identifying possible environmental exposures. We also provide clinical information on the epidemiology, clinical presentations, treatment and prevention of pesticide exposures.
  [Sanborn, MD, D Cole, A Abelsohn, and E Weir. May 28 2002. CMAJ 166 (11): 1431-1436]
• Exposures of children to organophosphate pesticides and their potential adverse health effects.
  Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children's exposure to pesticides and other environmental agents, and thereby reduce the incidence of environmentally related disease.
  [Eskanazi, B, A Bradman, and R Castorina. 1999. Environmental Health Perspectives 107(Suppl 3): 409-419]
• Five office workers inadvertently exposed to cypermethrin
  Five cases of poisoning by cypermethrin, a pyrethroid pesticide, are presented. The chemical was inadvertently introduced to the air-conditioning ducts and the patients inhaled it. Exposed patients experienced shortness of breath, nausea, headaches, and irritability. The exposure was compounded by repeated entry into the contaminated area and slow referral to a physician experienced in pesticide exposures.
  [Lessenger JE. 1992. J Toxicol Environ Health 35: 261-267]
• Indoor spraying with the pyrethroid insecticide lambda-cyhalothrin: effects on spraymen and inhabitants of sprayed houses.
  In March 1990 a study was carried out in the village of Kicheba, United Republic of Tanzania, in which the pyrethroid insecticide lambda-cyhalothrin was sprayed on all the internal surfaces of houses and other shelters at a coverage of about 25 mg of active ingredient per m2. All the spraymen complained at least once of symptoms that were related to exposure to lambda-cyhalothrin, the commonest being itching and burning of the face, and nose or throat irritation frequently accompanied by sneezing or coughing. Facial symptoms occurred on non-protected areas only. The number of subjects affected and the duration of their facial symptoms were proportional to the amount of compound sprayed.
  [Moretto A. 1991.Bull WHO 69 (5): 591-594]
• Occupational exposure to some synthetic pyrethroids (permethrin and fenvalerate).
  In a two-step study on exposure control method for occupational handling of permethrin was developed. Air sampling on a filter can be used in case of exposure to permethrin in powder form. The detection limit is 0.001 mg/m3. If biological sampling is used, the acid metabolite moiety in the urine must be monitored. However, the uptake after exposure to permethrin in forestry was too low, and no urine concentration could be found. The detection limit is 0.1 microgram/ml. Six persons in a plant nursery and six planters were studied in this way. Interviews were conducted with 139 planters. Irritative symptoms form the skin and upper respiratory tract were reported in 73% for fenvalerate, 63% for permethrin (trans/cis 75/25) and 33% for permethrin (trans/cis 60/40).
  [Kolmodin-Hedman, B, A Swensson, and M Akerblom. 1982. Arch Toxicol 50: 27-33]
• Insecticides: household use and respiratory impairment
  An early study done in the 1960s in Hawaii shows that frequent household use of insecticides is correlated with an increased prevalence of respiratory disorders, including asthma and chronic bronchitis. The majority of the household pesticides used were insect sprays for mosquitoes, flies, and cockroaches
  [Weiner, BP, and RM Worth. 1969. Hawaii Medical Journal 28 (4): 283-285]