A study supporting a link between insults to tracheal cartilage and development of pneumonia

As I've blogged a few times now, I think there is an overlooked component of respiratory tract cartilage harm contributing to who develops pneumonia in many contexts, including that of infection with the current headline-making virus. Here is the abstract of a 2019 study out of Saudi Arabia that supports such a hypothesis because it found that moving an endotracheal tube around after an initial placement thereof approximately tripled the risk of developing ventilator-associated pneumonia:

Repositioning of endotracheal tube and risk of ventilator-associated pneumonia among adult patients: A matched case-control study

Taha Ismaeil, Latifah Alfunaysan, Nouf Alotaibi, Shatha Alkadi, and Fatmah Othman
Ann Thorac Med. 2019 Oct-Dec; 14(4): 264–268. doi: 10.4103/atm.ATM_26_19 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784441/)

Abstract:

INTRODUCTION:
Ventilator-associated pneumonia (VAP) is one of the most serious hospital-acquired infections to occur among mechanically ventilated patients. Many risk factors for VAP have been identified in the literature; however, there is a lack of studies examining the association between endotracheal tube (ETT) repositioning and an increase in the risk of VAP. The aim of the present study, therefore, was to investigate the effect of ETT repositioning and the risk of developing VAP.

METHODS:
Matched case-control studies were conducted among mechanically ventilated patients admitted to the intensive care unit (ICU) at King Abdulaziz Medical City from 2016 to 2018. Patients who had a documented VAP diagnosis were identified and matched to four controls (within a 10-year age band). The history of ETT repositioning (defined as changes in the positioned ETTs from the first reading at the time of ETT insertion) was explored in the medical files of the sample, as were other demographic and comorbidity risk factors. Logistic regression analysis was used to test the association between ETT repositioning and VAP.

RESULTS:
A total of 24 cases were identified with documented VAP diagnosis during the study. Those cases were matched to 81 controls. The mean age was 55 (standard deviation 21) for both cases and controls. VAP patients had a greater history of ETT repositioning (46%) compared to controls (29%). Patients who had a history of ETT repositioning were twice as likely to develop VAP as patients who had no history of ETT repositioning (P = 0.13). After adjustment of a potential confounder, the results showed evidence of an increased risk of VAP after ETT repositioning (odds ratio 3.1, 95% confidence interval 1.0–9.6).

CONCLUSION:
Reposition of ETT considers as a risk factor for VAP in ICU patients, and appropriate measures should be applied to reduce movements of the ETT tube.

Why are Laos and its neighbors faring so well during the COVID-19 pandemic? A consideration of diet factors

Laos had COVID-19 cases very early in this pandemic. Laos neighbors China and has many commercial ties to it. Yet Laos has had only 19 known cases and no deaths. Vietnam and Cambodia, which border Laos to the south and east, have had 387 cases total but also no deaths. And Thailand, at around 2500 known cases, has only seen 40 deaths. What is different about the Indochinese peninsula that could be protecting them from the case numbers  and death rates being experienced in Italy, Spain, and the USA?

I will leave the specialized research into biomedicine to the experts right now and focus on dietary differences. Food choices often make an enormous difference in health issues, and I don't see them getting much attention right now.

What do people eat in Laos? The main starches appear to be rice (especially glutinous rice) and fruit (especially papaya and banana). The primary dietary fats appear to be palm oil and coconut. Stir frying at a high temperature in a wok, grilling, and deep frying are the main ways in which food is cooked. Typical condiments include fish sauce, fermented shrimp paste, and soy sauce. While meals are often accompanied by many fresh greens, Laotians also eat sweet snacks throughout the day. Galangal (a close relative of ginger) is a heavily-used spice, along with garlic, shallots (a type of onion), and lemongrass. Green tea and coffee are common beverages.

How does the Laotian diet differ from the Italian diet? Ginger is not very popular in Italy. The main dietary starch is wheat. Green tea tends to be reserved for weight loss and fighting colds. Wine is commonly consumed. Olive oil is a cornerstone of the Italian diet. A variety of cooking methods is used, but wok usage is rare.

These are just some of the differences between typical Laotian and Italian diets. Which ones could be relevant to COVID-19? I want to point out three differences that I think should be investigated:

1) Ginger/galangal consumption.

Ginger is an anti-inflammatory spice. Ginger has repeatedly been shown to reduce the levels of both interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), cytokines which are involved in the destructive immune reaction to COVID-19. (See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103735/.)

2) Fermented shrimp paste. 

Shrimp shells are a good source of glucosamine, and the fermentation process breaks down the shell and thus makes the glucosamine more bioavailable. As I've discussed before on my blog, glucosamine appears to help protect against developing pneumonia, which I hypothesize is a result of its protecting cartilage cells from attack by the immune system. 

3) Lauric acid and myristic acid intake.

The "tropical oils," i.e., coconut oil and palm oil, contain lauric acid and myristic acid, which can help protect cartilage. (See https://www.oarsijournal.com/article/S1063-4584(18)30141-9/fulltext.) Lauric acid is relatively uncommon outside of coconuts.

Until recently, the Mediterranean diet was touted as one of the heathiest in the world. As seen in the past two months, it did not appear to protect the relatively wealthy countries of Italy and Spain from COVID-19, especially when compared to some financially-challenged countries in southeast Asia. I hope to see more attention paid in the coming weeks to possible dietary factors behind that unexpected outcome.

(My apologies for having almost certainly missed some other important dietary factors that could end up being relevant to the fight against COVID-19. The above is what I have put together from having lived in Europe and the Philippines and read a lot about southeast Asian and European cuisines. I even had an Italian live with our family recently, who made it clear that ginger was not a favorite with her!)

Hypothesis: Cartilage protection is connected to preventing development of pneumonia, especially that caused by COVID-19

I think there is an overlooked cartilage connection to the development of fatal pneumonia. Below I will point to how this hypothesis is supported by the current COVID-19 epidemic.

First, why a cartilage connection? Because in the 1918 influenza epidemic, a doctor's record indicates that those recovering influenza patients who sat up, ate solid food, and brought on coughing by being in smoke-filled rooms, quickly relapsed and died of pneumonia while patients who stuck to liquid diets and lay flat survived. (See https://www.archives.gov/exhibits/influenza-epidemic/records/visiting-doctor-letter.pdf) Hyaline cartilage is found in the trachea, larynx, and bronchi.

A longitudinal study looking at glucosamine--a shellfish component that is taken to protect against cartilage damage--found that glucosamine supplementation was associated with reduction of mortality from all causes and was associated with a very marked reduction in mortality from respiratory illnesses. (See https://link.springer.com/article/10.1007/s10654-012-9714-6)

If such a cartilage connection exists, why has it not been noticed by medical researchers previously? Conventional wisdom until recently has been that cartilage is "immune-privileged," i.e., that it is not attacked by the immune system even when cartilage cells are infected with a virus. Recent arthritis research indicates that the immune system does sometimes attack and cause destruction of cartilage cells. (E.g., https://www.nature.com/articles/s41598-018-36500-2 and https://www.nature.com/articles/srep16674) This points to an overlooked research avenue for pneumonia researchers.

Why should COVID-19 researchers spend precious time looking into this possibility when there are so many research areas they could be focusing on? Because environmental clues are pointing us to glucosamine and have since Chinese New Year travelers first left Wuhan carrying COVID-19 with them. 

COVID-19 is a highly contagious virus. China is highly connected via established tourism, trade, and other travel patterns to the countries of southeast Asia. Thailand, the Philippines, Vietnam, and Cambodia all had COVID-19 contacts and cases early in this pandemic. All are countries with densely populated areas and very poor infrastructure to support sanitation measures and any widespread ventilator needs. Why do they still have so few deaths compared to European countries and the USA? Vietnam and Cambodia still have no fatalities at all. Consider that for a moment: Cambodia and Vietnam combined have had nearly as many cases but far fewer deaths (i.e., zero) than Hawaii.

One reason could have been that those four southeast Asian countries are warmer countries. But tiny Singapore is warm. Spain and Italy are not snowbound in March. Louisiana, one of the hardest-hit US states, is a warm place. And, of course, Hawaii is very warm.

These four southeast Asian countries share a common dietary element that is mostly unused outside of that region: fermented shrimp paste. Shrimp paste is a very good source of readily bioavailable glucosamine. Shrimp paste is integral to meals in both Cambodia and Vietnam. It is commonly, though not universally, used in Thai cooking. Shrimp paste is a frequently used condiment in the Philippines, especially as a companion to green mango slices. A survey of the COVID-19 statistics supports a conclusion that consumption of fermented shrimp paste in the national diet is inversely related to COVID-19 case and mortality burdens.

Glucosamine is a widely used supplement--so it has a track record for safety already--that can be easily administered. There is vegetarian glucosamine available for those with shellfish allergies. In order to maximize its absorption by the surfaces of the upper respiratory tract, glucosamine can be included in warm broths and/or sucked on in the mouth to permit it to be aerosolized to some degree. Nebulizer administration appears to be a possible option for administration of glucosamine directly to the bronchi.

It’s worth investigating this hypothesis. The cost to test glucosamine's helpfulness in controlling COVID-19 symptoms is as minimal as you can get for a medication, and the potential benefit is huge in light of Vietnam and Cambodia’s continuing lack of fatalities from COVID-19. 

Disclaimer: I have no profit motive in posting this. I am an independent researcher who has lived on four continents and researches how regional diet differences could be connected to the epidemiology of various health issues.