Asthma: Is it really untreatable?

Asthma is a common autoimmune disease that usually occurs in childhood. Adult asthma patients often develop the disease from childhood until they grow up, but some patients first develop asthma in adulthood or even in old age. Asthma symptoms are manifested in respiratory constriction, swelling and sputum production, leading to wheezing, shortness of breath, chest tightness, coughing… In severe cases, excessive constriction of the respiratory tract may lead to suffocation.

A study on asthma published in The Lancet in 2018 is the most comprehensive review and prospect of asthma in recent years. Currently, there are two main goals for long-term clinical treatment it:

1) Minimize symptom burden on daily life, including reducing daily symptoms and reducing the impact on sleep and other activities;

2) Reduce the risk of adverse asthma outcomes, such as airway obstruction

Therefore, as of today, the opinions of mainstream medical experts are that there is nothing else that can be done except to hope to reduce asthma symptoms and avoid major accidents. Asthma patients know that carrying asthma steroid sprays and oral steroid drugs is a matter of life and death. What we are discussing today is the latest research on asthma, and the progress of non-drug methods in treating asthma.

In recent years, there is a so-called “hygiene hypothesis” for various allergic symptoms including asthma. According to the theory of the hygiene hypothesis, due to insufficient exposure to pathogens and various bacteria in childhood, including good bacteria such as probiotics or bad pathogens, the normal development of the immune system is affected, and the possibility of allergic diseases such as asthma is increased. Therefore, if children are allowed to play freely on the ground, food is not too hygienic, and even the use of dishwashers is reduced, it may be possible to reduce excessive hygiene, thereby reducing the risk of children suffering from asthma and allergic diseases. However, the hygiene hypothesis cannot well explain the findings of many epidemiological studies, such as:

1) Japan is an extremely clean country compared to other countries, including Europe and the United States, but the number of asthma cases in Japan is much lower than in Europe and the United States;

2) In developed countries such as the United States and Australia, the lower class people have a high probability of contracting various infectious diseases, but they also have a high probability of suffering from asthma;

3) Having an infectious disease in childhood does not reduce the risk of developing asthma.

Therefore, the hygiene hypothesis does not seem to explain the increasing incidence of asthma and allergic diseases. [3] Recent epidemiological studies have shown that dietary structure, including the mother’s diet during pregnancy, [4] is more closely related to asthma and allergic diseases.

antibiotic

A recent animal experiment published in February 2020[5] found that children born to mothers who took antibiotics during pregnancy were much more likely to develop asthma. The researchers fed pregnant mice the broad-spectrum antibiotic vancomycin and found that the severity of asthma in the offspring was positively correlated with the dose of antibiotics taken. Further analysis found that the intestinal flora of the offspring was very different from that of ordinary mice. The researchers concluded that antibiotics taken during pregnancy change the intestinal flora of the next generation, increasing the probability of asthma and lung inflammation in the next generation.

In 2019, Canadian scholars published a prospective cohort study [6] that compared the use of antibiotics and asthma cases. The researchers analyzed 2,644 children in British Columbia, Canada, and compared the relationship between taking antibiotics before the age of 1 and the onset of asthma. The researchers found that between 2000 and 2014, the number of children aged 1-4 years with asthma decreased by 7.1 cases per 1,000 children to an average of 20.2 cases, a decrease of 26%.

The number of antibiotics prescribed by doctors to these children before the age of 1 also decreased, from 1,253.8 doses per 1,000 children to 489.1 doses. A careful analysis showed that the proportion of children who had taken antibiotics and had asthma was: 5.2% for those who had not taken antibiotics, 8.1% for those who had been prescribed 1 dose, 10.2% for those who had been prescribed 2 doses, and 17.6% for those who had been prescribed 3 doses. Therefore, the risk of developing asthma before the age of 5 years has a significant positive correlation with the dose of antibiotics prescribed before the age of 1 year. For every 10% increase in prescribed antibiotics, the probability of developing asthma increases by 24%.

Only two representative studies are listed above. The disruption of intestinal flora caused by antibiotics has received increasing attention in recent years. Below you will see the relationship between intestinal flora and asthma.

Fat

The amount and composition of different fats in the diet have a significant impact on the onset of asthma. A 2019 Portuguese study of 699 elementary school students with an average age of 9[7] found that the amount of fat intake in overweight children was positively correlated with the onset of asthma. The researchers concluded that diet is closely related to the onset of asthma. Based on the results of the study, increasing the intake of fruits and vegetables to balance fats can help alleviate asthma, especially for obese children with asthma.

A 2017 meta-analysis[8], which included 15 epidemiological studies, found that a Mediterranean diet high in olive oil was inversely associated with asthma. A 2019 Italian epidemiological study[9] found that olive oil containing oleic acid was associated with a reduced incidence of asthma. The 25% of people who consumed the least olive oil had twice the risk of asthma compared to the 25% who consumed the most olive oil. The researchers further quantified the risk and found that increasing the intake of olive oil by 10g (note: about 2 teaspoons) per day reduced the risk of asthma by 20%.

As early as 2000, a randomized controlled clinical study proved that omega-3 fatty acids are effective in treating asthma[10]. 29 children with asthma took fish oil containing 120 mg of DHA/EPA every day for 10 consecutive months, while the control group took a placebo (olive oil). The results showed that the group taking fish oil had significantly improved asthma symptoms and increased sensitivity to asthma drugs. The control group did not show any significant improvement. It is worth noting that this study may be considered an early study, and the dose of fish oil used is very conservative in my opinion, only equivalent to 400 mg of 30% pure fish oil.

A 2019 cross-sectional study [11] analyzed 255 adult subjects with asthma and found that among asthma patients, the more DHA/EPA in their blood, the easier it was to control their asthma and the lower the dose of hormonal spray medication they used.

Unhealthy fats are not asthma-friendly. Switching to olive oil, increasing omega 3, and reducing other fats in the diet can help with asthma.

Vitamin A

The Vitamin A, also known as retinol, is a fat-soluble vitamin essential to the human body. Vitamin A can be absorbed directly from animal foods. For example, animal liver, milk and eggs contain more vitamin A, while meat contains less. Plant foods, such as carrots, tomatoes and various vegetables, contain carotene, which can be converted into vitamin A in the human body, but the conversion efficiency is not very high. Vitamin A has a good effect on the treatment of asthma. Vitamin A reduces the occurrence of inflammation by regulating the immune system. For example, vitamin A can simultaneously reduce the body’s oxidative stress response and the inflammatory Th2 cell response, and increase the number of Treg cells that reduce inflammation, thereby reducing the body’s inflammatory response, especially in the respiratory tract. [12]

Animal experiments have shown that vitamin A supplementation can help prevent the occurrence of asthma [13]. Infection with Streptococcus pneumoniae during the birth period increases the probability of developing asthma later in life. Studies have found that infection with Streptococcus pneumoniae also significantly reduces vitamin A in the lungs, and the body is also deficient in vitamin A. Studies have also found that mice infected with Streptococcus pneumoniae not only have a significant reduction in vitamin A, but also a significant increase in inflammatory immune cells. After supplementing vitamin A with mice infected with Streptococcus pneumoniae, the number of inflammatory immune cells in the mice is significantly reduced, and the number of inflammatory immune cells in the respiratory tract and lungs of mice supplemented with vitamin A is also less than that of mice not supplemented with vitamin A.

In 2010, Chongqing Medical University conducted a study on newborns with wheezing[14]. They examined 311 infants with wheezing. Among infants with persistent wheezing, 34.1% were severely deficient in vitamin A and 39.0% were moderately deficient in vitamin A. Among infants with acute wheezing, 16.4% were severely deficient in vitamin A and 29.0% were moderately deficient in vitamin A. Comparing the two types of infants with wheezing, the vitamin A deficiency was more severe in infants with persistent wheezing, and the degree of vitamin A deficiency was positively correlated with wheezing symptoms. The conclusion of the study is that vitamin A deficiency may be related to the occurrence and severity of wheezing in infants.

In 2009, a clinical study conducted by doctors in Changzhou City observed the clinical efficacy of vitamin A in the adjuvant treatment of infantile asthma. 80 asthmatic children were divided into a vitamin A adjuvant treatment group (40 cases) and a conventional treatment group (40 cases), and a control group of 40 healthy infants. Both groups of asthmatic children were given glucocorticoids and bronchodilator inhalation treatment, and the vitamin A adjuvant treatment group was given vitamin A.

After observing the changes in the severity of asthma attacks in the two groups of children, the results showed that adding vitamin A had a positive effect on the severity of asthma attacks compared to conventional treatment alone. The conclusion of the study was that vitamin A can reduce the frequency of asthma attacks in infants and young children and reduce the severity of asthma attacks. It is recommended to use vitamin A to assist in the treatment of asthma in infants and young children.

An epidemiological study in 2009[15] compared 433 children and adolescents aged 6-18 with asthma and 537 healthy people of the same age. It found that there was no difference in beta-carotene, cholesterol, triglycerides, etc. between the two groups. The only difference was vitamin A, which was significantly lower in the asthmatic group than in the healthy group. The conclusion of the study was that the lower vitamin A level in children with asthma may be related to the development of asthma.

A 2011 meta-analysis [16], which included 62 studies, concluded that asthma patients have lower levels of vitamin A. Although this was only an epidemiological study and not a more robust clinical study, there is evidence to support that supplementation with nutrients including vitamin A (others include vitamin D, E, vegetables, and the Mediterranean diet) may be effective in preventing asthma.

There have been no direct clinical trials on the effects of vitamin A on asthma[17], but clinical trials on the effects of vitamin A on lung function and respiratory diseases show that vitamin A has a significant effect on respiratory diseases. A randomized controlled trial conducted by scholars from Sichuan University on 100 patients with chronic lung disease in China in 2012 found[18] that a group of patients who took 10,000 IU of vitamin A daily for 6 consecutive months had significantly improved lung function and walking distance compared to the control group who did not take vitamin A. Pulmonary function tests, including FEV/FVC, were also improve. There were no adverse reactions to taking this dose of vitamin A.

Due to the lack of strong evidence from randomize control clinical studies, vitamin A supplementation is not recommend clinically. My interpretation of the study is that vitamin A deficiency is probably not the direct cause of asthma, but as an antioxidant, asthma patients may consume a lot of vitamin A under the influence of inflammation, and vitamin A has a significant effect on respiratory diseases. Vitamin A supplementation is likely to improve asthma symptoms.

Vitamin D3

Strictly speaking, vitamin D3 is a hormone rather than a vitamin, because the cholesterol derivative under the human skin can be synthesize by the body after exposure to ultraviolet light. Vitamin D3 is the precursor of 25-hydroxyvitamin D (25-hydroxyl Vitamin D), which can also be understand as D3 being inactive and must be metabolize into 25-hydroxyvitamin D by enzymes in the liver and kidneys before it can have an effect in the body. Vitamin D receptors are widely distribute in the body. After entering cells, vitamin D can activate more than 900 genes, some of which control tumor formation and some can reduce inflammation. [19]

A clinical study in 2019[20] analyzed 29 children with mild asthma and 30 children with moderate asthma and compared them with 38 healthy children in the control group. It was found that the vitamin D levels in the blood of children with asthma were lower. The bronchoreography (bronchodilator reversibility), which assesses the severity of asthma, was inversely correlate with the level of vitamin D, indicating that the lower the vitamin D level, the more severe the asthma. The conclusion of the study is that low vitamin D is more common in children with asthma, and vitamin D is associate with bronchoreography (bronchodilator reversibility), which assesses the severity of asthma.

In 2016, Chinese doctors conducted a controlled clinical study on vitamin D. Fifty children under the age of three with asthma were divide into an intervention group and a control group. The control group received conventional treatment, while the intervention group received vitamin D on top of conventional treatment. The results showed that after adding vitamin D, the children’s recovery time, such as time to wheeze disappearance, time to dyspnea, and time to chest tightness, was shorter than that of the control group that only received conventional treatment. The conclusion of the study doctors was that vitamin D is effective in treating asthma in young children and is worthy of clinical promotion.

A 2016 systematic review [22] analyzed 7 double-blind controlled trials in children and 2 in adults, with a total of 435 children and 658 adults with asthma. The study quantified that vitamin D can reduce the use of cortisol sprays for asthma by 36% and reduce the chance of going to the hospital for acute asthma attacks by 61%. The conclusion of the study is that although it is not clear how to apply this research evidence in clinical treatment of asthma, the researchers believe that the evidence has shown that vitamin D is effective in reducing the incidence of asthma.

Canada is currently conducting the largest clinical trial to date on the effects of vitamin D on asthmatic preschool children (865 subjects) [23]. The trial has entered its third phase. The first phase was a pilot clinical trial conduct in 2013, which only tested the safety of 55 preschool children. The children took 100,000 IU of vitamin D3 at one time (author’s note: D3 generally contains 1000-4000 IU per pellet. The trial was equivalent to letting preschool children finish a bottle of D3 at one time, proving that D3 is very safe). They were then supplement with 400 IU per day for 6 consecutive months. The first phase only proved that high doses of D3 are also safe for preschool children, and that supplementing with D3 can immediately increase the level of vitamin D in the blood.

However, after a few months, no significant difference was found between the vitamin D levels of the children in the intervention group and those in the control group. The second phase of the clinical trial was publish in 2019. This time, the children took 100,000 IU, and then took another 100,000 IU 5 months later. The results showed that 7 months after taking the first dose of vitamin D3, only 56% of the children could maintain adequate vitamin D levels, proving that children with asthma consume a lot of vitamin D.

The study once again proved that high doses of vitamin D are safe and necessary for children with asthma. The study is still ongoing. My personal interpretation is this: Asthma is the result of inflammation in the body, and the process consumes a lot of vitamin D. The association between asthma and vitamin D has been prove in previous studies.

Although it is only for preschool children, a one-time high-dose vitamin D supplement, or combined with a daily supplement of 400 IU of vitamin D, is safe, but not enough to restore children’s vitamin D to normal levels. Is it safe to continue to increase the dose? Will increasing and successfully maintaining vitamin D at normal levels help preschool children with asthma? The answer awaits the results of continued research. I personally tend to believe that inflammation consumes different vitamins and antioxidants in the body. What is adequate tolerance in healthy people becomes a drop in the bucket in sick people. Increasing the dosage may be safe and useful.

Vitamin D has accumulate a certain amount of clinical research on the treatment of asthma, which has been prove to be safe and effective. My opinion is that vitamin D, like A, will be reduce in asthma patients due to inflammation. Supplementing vitamin D can also improve symptoms in the treatment of asthma.

Probiotics and soluble dietary fiber

The microbiome and microorganisms are closely related to the onset of asthma[24]. The microbiome affects the human body through three pathways. The first is the environment, such as dust mites in the home and microorganisms of different livestock in rural areas. The second pathway is the microbiome in the respiratory tract and lungs. Evidence has shown that bacteria and microorganisms such as streptococci in the respiratory tract affect respiratory inflammation. The third pathway is the intestine. The “gut-lung axis” has received increasing attention in recent years. The intestinal flora affects the occurrence and severity of asthma. Today we focus on the third pathway, how to prevent and improve asthma by affecting the intestinal flora.

A recent study published in February 2020[25] analyzed the gut-lung axis. The gut-lung axis is a conclusion draw by researchers from their observations of asthma in recent years. Numerous research results show that the intestinal flora has a great impact on the respiratory microenvironment of asthma, and the intestinal flora of asthma patients is very different from that of healthy people. Studies have found that the imbalance of intestinal flora in asthma patients during childhood may lead to the occurrence of asthma in the future.

Although it is not clear how the intestine and the respiratory tract “communicate”, the epithelial cells of the respiratory tract can receive remote information and then secrete different inflammatory cytokines, and immune cells can affect the lungs and respiratory tract through the lymphatic system after being stimulate by the intestine. The immune cells of the respiratory tract also have receptors to receive information transmitted from the intestine. The gut-lung axis is a two-way “communication”. Animal experiments have confirmed that stimulating the lungs of mice with endotoxin (LPS) can lead to a large increase in the intestinal bacteria of mice. Studies have also shown that pneumonia can cause intestinal damage.

When it comes to intestinal flora, people who have some knowledge of the intestines will first think of adjusting the intestinal flora through probiotics. After all, this is the direction of many popular science studies at home and abroad in recent years. A 2019 meta-analysis [26] included 19 randomized controlled clinical trials with a total of 5,157 children and found that probiotic supplementation had no significant effect on preventing or improving asthma. The conclusion of the study was that it is not clinically worth recommending that infants take probiotics to prevent asthma.

A 2019 meta-analysis [27] included 17 randomized controlled clinical trials with a total of 5,264 pediatric subjects and found that probiotic supplementation had no significant difference in preventing asthma compared with the control group. However, the study conclude that the effectiveness of probiotic supplementation in preventing asthma depends on what similar probiotics are supplement. For example, Lactobacillus rhamnosus GG can reduce the frequency of asthma attacks to a certain extent.

The use of probiotics does not seem to have a significant effect on improving the flora and asthma. So how about improving the intestinal flora and thus improving asthma? In a clinical study published by Australian scholars in 2019 [28], 17 asthma patients underwent three 7-day clinical trials, taking probiotics (three types: Lactobacillus acidophilus LA-5, Lactobacillus rhamnosus GG strain, Bifidobacterium infantis BB-12), or soluble dietary fiber (12 grams of inulin), or probiotics plus soluble dietary fiber every day for 7 consecutive days. The results showed that taking soluble dietary fiber can improve respiratory inflammation, asthma and intestinal flora. The conclusion of the study is that it is worth further studying the role of soluble dietary fiber in managing asthma.

How does soluble fiber work? Probiotics in the intestines need to ferment soluble fiber, and the metabolites include different short-chain fatty acids (SCFA), such as acetate, propriontate, and butyrate. Many organs and tissues in the body, including the respiratory tract, have receptors for SCFA, and by stimulating the receptors of the respiratory tract (such as GPR41, GPR43) through SCFA, inflammation of the respiratory tract can be reduce. Let’s look at the results of a trial that only took soluble dietary fiber once.

In a pilot clinical trial in 2017[29], 29 adult asthma patients were test and took 175g of yogurt, 3.5g of inulin, and a combination of probiotics (three types: Lactobacillus acidophilus LA-5, Lactobacillus rhamnosus GG strain, and Bifidobacterium infantis BB-12). The results show that 4 hours after taking the above combination of probiotics and prebiotics, the number of inflammatory immune cells in the sputum of the intervention group was significantly reduce, and the maximum force expiratory volume (FEV) for assessing the severity of asthma was significantly improve. The conclusion of the study is that a single supplement of soluble dietary fiber has been show to improve respiratory inflammation and asthma indicators, and long-term supplementation of soluble dietary fiber may be more helpful for asthma.

What about the effect of a multi-pronged approach? In 2012, scholars from Taiwan conducted a double-blind controlled clinical study [30]. 192 primary school students aged 10 to 12 with asthma were divide into an intervention group and a control group. The intervention group took three health supplements every day for 16 consecutive weeks: fish oil, antioxidants extracted from vegetables and fruits (400 mg, equivalent to 2 servings of vegetables and fruits), and probiotics (Lactobacillus salivarius). The control group only took a placebo. The results show that the lung function of the children in the intervention group was significantly improve.

The remarkable part of this clinical trial is the high dose of omega 3. A large child weighing 45-60kg takes 1775mg of DHA/EPA per day. Assuming that the purity of the general fish oil pills is 30%, it is equivalent to taking 6 1-gram fish oil pills. If the fish oil pills with a purity of no less than 60% are use as I generally recommend (the study used fish oil pills with a purity of 70%), it is also about 3 grams. This trial also proves that fish oil is a very safe supplement even for children. A higher dose can be use, and a small dose may not be effective.

Another feature of this study is that it used purified antioxidants from vegetables and fruits, proving that vegetables and fruits not only prevent and treat asthma through dietary fiber, but also the antioxidants in them can produce therapeutic effects.

A 2014 study showed[31] that eating more vegetables and foods with anti-inflammatory nutrients can help improve asthma. A 2013 study[32] analyzed the dietary structure of asthma patients and healthy people and found that patients with severe asthma consumed more fat than dietary fiber on a daily basis. For asthma patients, the more fat and less dietary fiber they consumed on a daily basis, the lower their FEV (author’s note: weaker lung function) and the more inflammatory cells in their respiratory tract. The conclusion of the study is that among asthma patients, the dietary habits of patients with severe conditions are significantly different from those of healthy people, and this dietary structure is associate with lung function and respiratory inflammation.

Studies have also shown that increasing exercise can help improve asthma[33]. Many asthma patients reduce or even completely avoid physical activity because they are afraid of an asthma attack. In fact, with proper arrangements, such as the company of family or friends and the preparation of emergency medications, increasing exercise will only reduce the risk of asthma. In addition, combined with the above-mentioned diet that reduces fat and increases dietary fiber, it can help reduce weight. For obese asthma patients, reducing 5%-10% of their weight is already a significant help in improving asthma[34].

Summarize

In mainstream medicine, asthma cannot be cure. We can only reduce the impact of asthma on daily life and prevent acute and severe asthma. However, we can draw the following conclusions from the latest research:

1. Reducing the use of antibiotics during pregnancy, infancy, and even adolescence can greatly help prevent asthma;

2. The bacterial flora is closely related to the occurrence of asthma, but simply supplementing with probiotics does not seem to solve the problem;

3. Increasing the amount of vegetable foods with dietary fiber and reducing the amount of foods with excessive fat can help prevent and improve asthma;

4. Among fats, omega-3 fatty acids and olive oil are helpful in improving asthma, while omega-6 fatty acids and saturated fats may increase the risk of asthma. Therefore, eating cold-water fish and seafood rich in omega-3 fatty acids can help prevent asthma and reduce the risk of asthma.

5 As asthma causes symptoms through inflammation, inflammation may also cause a large reduction in the body’s vitamin A and vitamin D. Supplementing vitamin A and vitamin D has a good effect on improving asthma symptoms. Taking cod liver oil, which contains a large amount of vitamin A and a small amount of vitamin D, is the best way to supplement vitamin A. Otherwise, the only way to get a large amount of vitamin A from food is to increase the consumption of animal liver. Although cod liver oil contains vitamin D, the dosage is limited. My personal experience suggests that an additional daily supplement of 4000 IU of vitamin D in the early stage and maintaining about 1000 IU thereafter may have a preventive effect on the onset of asthma.

6 If you cannot eat cold-water fish regularly, taking high-purity fish oil pills after meals (fish oil and cod liver oil are different nutrients, although cod liver oil contains a small amount of omega 3) can help prevent asthma. I recommend taking at least the same dosage as the Taiwanese scholar mentioned above, that is, at least DHA+EPA > = 1800mg = 3000mg of high-purity fish oil (60%) per day. This dosage is design for larger elementary school students, and you can adjust it according to your weight.

7 In addition to dietary fiber from dietary sources, additional supplementation of soluble dietary fiber, such as inulin, may help improve intestinal flora. Adding the probiotic combination used in the above study is also possible, but the effect may not be as important as that of soluble dietary fiber.

Is there no cure or is there a cure without medicine? At least we see hope from the latest research.

The content of this article is provided only as popular science knowledge and cannot replace the doctor’s treatment diagnosis and advice.