Medical Bulletin 08/ August/ 2024

In a recent study published in the journal Cell, a team of researchers in the Netherlands analysed nasopharyngeal, oropharyngeal, and saliva samples across various age groups and analysed the microbial composition of these samples to determine the association between the microbiota in the upper respiratory tract and the health of the host and environmental factors.

There is now extensive evidence showing that microbial communities within the human body are crucial for health and disease. Although much of the research has concentrated on the gut microbiome, studies have demonstrated that the microbiome of the upper respiratory tract is closely connected to respiratory health. It plays a significant role in influencing susceptibility to respiratory infections.

In this study, researchers examined the microbiome composition and diversity in nasopharyngeal, oropharyngeal, and saliva samples from a cross-section of the Dutch population. Their aim was to characterise changes in the upper respiratory tract microbiome across different stages of life and investigate its associations with the host and environmental factors.

The researchers also conducted a complete linkage hierarchical clustering analysis to investigate the community structures within the oral and nasopharyngeal niches. Furthermore, they explored the relationship between variations in the upper respiratory tract microbiome and various environmental factors, including the season of sampling, socioeconomic status, lifestyle, antibiotic use, diet, household composition, and contact with animals, children, elderly individuals, or patients in a work setting.

The study found that the microbiome composition in the upper respiratory tract, especially in the nasopharyngeal niche, was strongly correlated with and underwent maturation with age. The upper respiratory tract microbiota also exhibited distinct patterns within different niches. The microbiome in the nasopharynx of younger individuals had a higher density of total bacteria but lower diversity.

In conclusion, the study examined the microbial composition and diversity within the upper respiratory tract's oral and nasopharyngeal niches. The results suggested that the upper respiratory tract microbiome showed development and maturation patterns associated with age and sex in the nasopharyngeal niche, while in the oral niche, the associations were with lifestyle factors such as tobacco, antibiotics, and alcohol use.

References: Odendaal, M., de, Franz, E., Mei, C., Groot, J. A., Logchem, van, Hasrat, R., Kuiling, S., Pijnacker, R., Mariman, R., Trzciński, K., van, Sanders, E. A. M., Smit, L. A. M., Bogaert, D., & Bosch, T. (n.d.). 2024. Host and environmental factors shape upper airway microbiota and respiratory health across the human lifespan. Cell. DOI:10.1016/j.cell.2024.07.008 https://www.cell.com/cell/fulltext/S0092-8674(24)00768-2

In a recent study published in The Lancet Public Health, researchers investigated the associations between early adulthood body mass index (BMI) and cardiovascular diseases and the effect of midlife lifestyle factors on these outcomes.

The study's findings suggest that a higher BMI in early adulthood is linked to an elevated risk of developing cardiovascular diseases. This highlights the importance of preventing obesity and managing weight during early adulthood to support cardiovascular health later in life.

The researchers tracked participants aged 30–79 from five urban and five rural regions. Between 2004 and 2008, they collected data through interviews, physical measurements, and written consent. The study excluded individuals with a history of heart disease, stroke, cancer, or diabetes at the start, as well as those who were not within the 35–70 age range or lacked BMI data for age 25. Participants self-reported their weight from early adulthood, and BMI was calculated using this weight and their height at baseline. Lifestyle factors, including smoking, drinking, physical activity, and diet, were evaluated through questionnaires.

After excluding individuals who had heart disease, stroke, transient ischemic attack, cancer, or diabetes, the final sample included 360,855 participants. The participants' average age was 50 years, with 42% male and 58% female. The participants had a mean BMI of slightly less than 22 kg/m² in early adulthood and nearly 24 kg/m² in middle adulthood.

Cardiovascular disease risk was positively associated with BMI during early adulthood, with participants having a BMI of over 30 kg/m² experiencing a 58% higher risk than those with a lower BMI. Obesity, defined as having a BMI over 28 kg/m² during early adulthood, was linked to a 39% higher probability of developing cardiovascular disease.

The study identifies the importance of weight management during early life in preventing cardiovascular disease, highlighting a need for initiatives targeting young adults. Future research should address early adulthood lifestyle factors and dynamic weight changes for a more comprehensive understanding.

References: Early adulthood BMI and cardiovascular disease: a prospective cohort study from the China Kadoorie Biobank. Chen, Y., Yu, W., Lv, J., Sun, D., Pei, P., Du, H., Yang, L., Chen, Y., Zhang, H., Chen, J., Chen, Z., Li, L., Yu, C., China Kadoorie Biobank Collaborative Group. The Lancet Public Health (2024). DOI: 10.1016/S2468-2667(24)00043-4, https://www.sciencedirect.com/science/article/pii/S2468266724000434

In a recent study published in the journal of clinical oncology, Researchers from The University of Texas MD Anderson Cancer Center demonstrated that adding metastasis-directed radiation therapy to standard-of-care chemotherapy improves progression-free survival (PFS) in patients with oligometastatic pancreatic cancer. At a median follow-up of 17.3 months, PFS was 10.3 months in patients who received metastasis-directed therapy (MDT) plus chemotherapy compared to only 2.5 months in those who received standard chemotherapy treatment. Additionally, increased immune responses from MDT were connected to longer survival times.

Metastatic pancreatic cancer spreads rapidly to vital organs, posing significant challenges for disease management. Diagnosis often occurs at an advanced stage, reducing treatment efficacy and decreasing survival rates. The disease's complexity and resistance to many therapies also contributes to its poor prognosis. Chemotherapy, the main treatment option, generally offers a seven-month average survival time before disease progression.

MDT targets metastases with high-dose ablative radiation therapy, aiming to eliminate all cancer cells at all sites identified on a scan. This approach is primarily being evaluated for patients with oligometastatic disease for whom imaging shows five or fewer metastases. Oligometastatic disease is often described as an intermediate stage of cancer, between a localised tumour and widespread cancer.

The median time to new lesion recurrence was 14 months in the MDT arm versus five months in the control arm. The 12-month freedom from new lesion recurrence rate was 54% in the MDT arm and 38% in the control arm. Crossover from the control arm to MDT was allowed. MDT, which primarily consisted of high-dose ablative radiation therapy, was very well tolerated, with no grade three or greater adverse events related to MDT observed.

The study's exploratory endpoints aimed to investigate the effects of MDT on the body's immune system, following earlier research demonstrating its potential to boost immune response. The researchers found that systemic immune activation events were associated with MDT and correlated with improved PFS.

The results suggested that metastasis-directed therapy is effective and safe for patients with oligometastatic pancreatic cancer. Nevertheless, larger trials are necessary to confirm the survival advantage observed with metastasis-directed local treatment and to investigate systemic immune activation as a potential mechanism for therapeutic benefits.

References: Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. [PubMed] [CrossRef] [Google Scholar]

A recent study published in The American Journal of Medicine Doctors recommend making fruits and vegetables a foundational part of the treatment of patients with hypertension. Diets high in fruits and vegetables are found to lower blood pressure, reduce cardiovascular risk, and improve kidney health due to their base-producing effects. Despite ongoing efforts to improve hypertension treatment and reduce its adverse outcomes with pharmacological strategies, hypertension-related chronic kidney disease and its cardiovascular mortality are increasing. Heart disease is the number one reason that patients with chronic kidney disease die.

The Dietary Approaches to Stop Hypertension (DASH) diet that is rich in fruits and vegetables reduces blood pressure and is the recommended first-line treatment for primary hypertension. Nevertheless, this diet is under-prescribed, and when prescribed is under-implemented despite supportive epidemiological data. The DASH diet and others generally high in fruits and vegetables are associated with lower blood pressure, lower risk for and progression of chronic kidney disease, lower cardiovascular disease risk indicators, and lower cardiovascular disease mortality.

To test this hypothesis, a study was designed in which participants with hypertension, but not diabetes, and very high levels of urine albumin excretion (macroalbuminuria) were selected. Patients with macroalbuminuria have chronic kidney disease, a high risk for the worsening of their kidney disease with time, and a high risk to subsequently develop cardiovascular diseases. In a randomised control trial over a five-year period, investigators divided the cohort of 153 patients with hypertension into three groups:

1. Study participants adding 2-4 cups of base-producing fruits and vegetables in addition to their usual daily food intake

2. Study participants prescribed NaHCO3 (acid-reducing sodium bicarbonate, which is common baking soda) tablets in two daily doses of 4-5 650 mg tablets

3. Study participants receiving standard medical care from primary care clinicians

The results of the study show that both fruits and vegetables and NaHCO3 improved kidney health, but only fruits and vegetables, and not NaHCO3, reduced blood pressure and improved indices of cardiovascular disease risk.

References: Joint National Commission on detection, evaluation, and treatment of high blood pressure. The fifth report of the Joint National Commission on detection, evaluation, and treatment of high blood pressure (JNC V). Arch Int Med 1993;153, 154-186.