The Ubiquitous Journey of Propylene Oxide

While Propylene Oxide (PO) may not be as infamous as some chemicals, its widespread use in industrial and consumer applications has made it a constant presence in our environment. Industries that rely on PO include those producing polyurethane polyols, propylene glycol, and fumigants.

The global market for Propylene Oxide estimated at $14.4 billion in 2020, is projected to reach $18.8 billion by 2027. Additionally, traffic emissions contribute to ambient levels of propylene, the precursor of PO, further underscoring its ubiquitous nature.

Recent research has revealed that many chemicals, including PO, leave more significant marks on the human body than previously thought. A new study by the Environmental Working Group (EWG) found chlormequat, a lesser-known pesticide, in 80% of people tested. Chlormequat chloride, used increasingly on grain crops in North America, has been linked to reduced fertility and developmental harm at doses lower than regulatory agencies' allowable daily intake levels. The study reported a significant increase in chlormequat concentrations in urine samples collected in 2023 compared to previous years.

A recent systematic review published on MedrXiv, titled "Biological Factors Influencing Individual Responses to Propylene Oxide," sheds light on the complex interplay between environmental exposures, genetic makeup, and individual susceptibility concerning PO levels in the human body. This review highlights the growing public health significance of propylene oxide beyond occupational exposure.

The study emphasizes the importance of considering individual variability in response to PO exposure, influenced by factors such as sex, dietary preferences, genetics, and physiology. It focuses on several genes (CYPs, mEH, GSTT1, GSTM1, FMO3, ADH, ALDH, GDHt) and microbes (including opportunistic pathogens, neutral or even beneficial bacteria) that could be relevant to PO metabolism reactivation and elimination from the body.

PO, primarily encountered through inhalation in occupational settings, poses potential health risks due to its genotoxic effects on DNA. The metabolism of PO primarily occurs through glutathione conjugation and epoxide hydrolase-mediated hydration, with interspecies differences noted. Furthermore, the human microbiome's role in PO metabolism highlights the complexity of individual responses, while environmental factors and seasonal variations further modulate PO's impact.

This comprehensive review stresses the limitations in our abilities to maintain and continuously update living reviews and indexing. It also emphasizes the importance of advancing AI capabilities in literature reviews to capture nuanced, indirect evidence more effectively. While AI tools like Elicit and Perplexity show promise, challenges persist in processing longer segments of information and ensuring consistency across platforms.

Moving forward, the development of specialized AI architectures tailored for systematic reviews is imperative. By enhancing AI tools strategically, we can navigate the complexities of scientific literature more effectively, enabling better summarization and addressing unanswered questions in environmental health research. This study paves the way for targeted research and technological innovation, advocating for a multidisciplinary approach to understanding individual responses to environmental chemicals like PO.

REFERENCES

Gabashvili, IS. Biological Factors Influencing Individual Responses to Propylene Oxide: A Systematic Review medRxiv 2024.02.15.24302622; doi: https://doi.org/10.1101/2024.02.15.24302622

Temkin, A.M., Evans, S., Spyropoulos, D.D. et al. A pilot study of chlormequat in food and urine from adults in the United States from 2017 to 2023. J Expo Sci Environ Epidemiol (2024). https://doi.org/10.1038/s41370-024-00643-4

Open-Source Project: OSF | Biological Factors that Influence Individual Responses to Environmental Epoxides DOI 10.17605/OSF.IO/W7682

Who Benefits the Least from the COVID-19 Vaccines

Factors associated with inadequate vaccine responses in patients with breakthrough infections are still not fully understood. Studies show that genes, environment (such as air pollution), and gene-environmental interactions all influence Coronavirus disease. Less research has been done for the vaccines. 

An earlier study [Boyarsky et al, 2021]  found that 46% of transplant patients had no antibody response after two doses of messenger RNA (mRNA) vaccines. Several medical case reports about fatal breakthrough  infections listed chronic migraine, obesity, autoimmune conditions,  diabetes, atrial fibrillation, myeloma (with anti-BCMA CAR-T therapy), arterial hypertension and old age among pre-existing conditions.  Some fatal breakthroughs, however, had no apparent underlying causes. 

A new study used real-world data to evaluate risk factors of impaired antibody response to SARS-CoV-2 mRNA vaccines in individuals with chronic medical conditions evaluated in a respiratory specialty clinic. The percentage of patients without antibodies detected was as follows:

- 14% in asthma 

- 15% in COPD

- 19% in Sarcoidosis

- 36% in Interstitial lung diseases

- 37% in Rheumatic diseases

- 48% in Congestive Heart Failure (CHF). 

More than a fifth of patients with chronic medical conditions may still have insufficient levels of antibodies to fight COVID-19 even after a second mRNA vaccine dose. Interstitial lung disease and congestive heart failure are two independent risk factors for low antibody response to COVID vaccination. These patients tended to be older — between 65 and 95 years old with a median age of 80.5 — and had preexisting comorbidities, such as cardiovascular disease and Type 2 diabetes. A subset of patients was also on immunosuppressive drugs that may affect vaccine efficacy. 

Anther study that analyzed fatal breakthrough cases came with the following risk order: Overweight/Obesity; Chronic cardiac disease; Diabetes mellitus, Chronic neurologic disease; Chronic kidney disease; Chronic liver disease; Chronic pulmonary disease; Immunosupression.  Pregnancy was shown to double the risk of breakthrough infection. 

Note that the mean age of study population was 62 years and the individuals received two doses of mRNA vaccines. Newer study shows that advanced age is one of major risk factors of fatal breakthrough COVID-19 even after an additional booster dose. 

CDC data, sourced from more than two dozen states, shows that between April and June, a total of 77,000 breakthrough cases and 1,500 breakthrough deaths were recorded, compared to more than 1.74 million breakthrough cases and 15,000 deaths recorded between July and the first week of November. It is unclear exactly how many of these people had also been boosted. As of October 12, 2021, there have been at least 31,895 individuals with SARS-CoV-2 breakthrough infections who were hospitalized or died in the United States. 

REFERENCES

Boyarsky BJ, Werbel WA, Avery RK, Tobian AA, Massie AB, Segev DL, Garonzik-Wang JM. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. Jama. 2021 Jun 1;325(21):2204-6.

Juthani PV, Gupta A, Borges KA, Price CC, Lee AI, Won CH, Chun HJ. Hospitalisation among vaccine breakthrough COVID-19 infections. The Lancet Infectious Diseases. 2021 Nov 1;21(11):1485-6.

Shu-Yi Liao et al, Impaired SARS-CoV-2 mRNA vaccine antibody response in chronic medical conditions: a real-world analysis, Chest (2022). DOI: 10.1016/j.chest.2021.12.654