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Chronic inflammatory diseases, the major health challenge in modern societies - Part 2


- The role of medical development beyond drugs: Self-care and disease prevention -

Wolfgang Kissel and Herbert Treutlein, 28 August 2018

In part 1 of this blog “Chronic inflammatory diseases, the major health challenge in modern societies” we have described the kind of tsunami of health problems coming towards us, especially in, but not limited to, industrial societies. In part 2, we go a bit further into chronic inflammatory disease and show with some examples what can be done to prevent and mitigate such diseases including ideas for self-care. 

When observing the R&D efforts by pharmaceutical companies in finding solutions for chronic inflammatory diseases one might expect that good therapies or even cures are available or at least on the horizon. But far from that. Inflammatory diseases are complex and even the best selling drug worldwide, Humira (treats Rheumatoid Arthritis) works only for 20-25% of the patient population and can have significant side effects.

Pharmaceutical companies will not stop searching for better drugs that’s for sure. The unmet medical needs are too many. However, shouldn’t be there other solutions, complementing solutions? Let’s face it, the pharmaceutical industry is focused on therapies for people who are ill and most therapies are for mitigating the disease condition and enable patients to get better and to manage the disease. Only few are able to cure a serious disease, which is anyway not too welcome by some “clever” analysts in the financial industry (Goldman Sachs asks: 'Is curing patients a sustainable business model?' ). 

Chronic inflammatory diseases are complex and most probably a drug, no matter how good the drug is, might not be enough. Therefore we need to look into additional measures to fight these diseases. Given the complexity, we cannot expect to find therapies where one size fits all. It needs multidisciplinary approaches from education to medical therapy. As emphasized in part 1 of this blog, the onset of chronic inflammatory diseases starts early in life and is sometimes undetected over decades. Only when we feel ill, we are looking for a therapy to help us getting healthy again. But this is exactly our problem. From what we know today, there is a range of proven measures that can support us in self-care and preventing the most debilitating stages of these diseases. Let us have a closer look at  examples of chronic inflammatory diseases that require a multidisciplinary approach and what we can do about it. Let’s start with maybe one of the biggest health threats we might not know about. 

NASH (Non Alcoholic Steatohepatitis)

NASH is a chronic inflammatory disease. It is a lifestyle disease and according to health experts is the fastest growing disease in industrial countries. It is considered as the biggest untapped area in medical care, however, largely unknown to the public (see The NASH Education Program). The reason for this is that it has no obvious symptoms, it currently can only be diagnosed by liver biopsy and there is no cure. More than 30 pharmaceutical companies are searching for the first drug to be approved, which is expected earliest by 2022-2028 (a quick overview NASH-Infographic, Pfizer and a detailed overview about NASH drug development: NASH BIOTECHS).

NASH is caused by constant inflammation triggered by excess fat in the liver. The precursor of NASH is NAFLD (Nonalcoholic Fatty Liver Disease) or commonly known as fatty liver. Via NASH, the disease develops into liver fibrosis, then further to cirrhosis (and some but not all into liver cancer). All the different stages of the disease from NAFL to liver cancer are strongly related to obesity. The prevalence of NAFLD among adults in industrial countries is above 30% and ca. 6% for NASH. For the USA this means ca. 18 million NASH patients and for a small country like Australia, ca.1.5 million patients. However, most of them don’t know that they might be at risk of NASH (remember: no symptoms). So how do we know? With its strong link to obesity and overweight we can make good estimations about who most probably is at risk for NASH. Other main risk factors are high blood pressure, high triglycerides, insulin resistance, type 2 diabetes, diet high in sugar (fructose), shift work (The Growing Epidemic of Non-alcoholic Steatohepatitis (NASH) Fatty Liver Disease, Pfizer). 

The accepted goals of any NASH treatment is to stop the primary inflammation, to stop liver cell degeneration and to stop subsequent inflammatory conditions (the good news is that the liver is the only organ that can regenerate, which gives it a good chance to reverse NASH). Knowing that NASH drugs are not available for at least the next 5 years, lifestyle modifications are the only way. Even when the drug(s) are available it is already known that only the combination of drug with lifestyle changes will be the only sustainable therapy. So, what do we do until then? 

Again, NASH is a lifestyle disease, meaning we can do a lot to prevent the disease by adapting our lifestyle accordingly. However as the awareness about the disease is very low, so why changing. Nevertheless, a multidisciplinary approach could look as follows:

  • Education and counselling can play a big role, starting with kids and their parents. NASH is the leading liver disease in children fueled by the growing childhood obesity epidemic. Schools should play a role by establishing lifestyle counselling/coaching into their curriculum. According to the old saying “You can't teach an old dog new tricks”, we start to learn new tricks (learning about lifestyle) when we are young. But this only works when parents are an active part of this and don’t leave it to institutions.
  • Self-care: People who assume to be at risk can take things into their own hand. The below mentioned lifestyle changes are a good compass. However, we all know how hard it is to change things we are used to. But you are not alone. People can do it together and support each other, like peer coaching, meaning controlling each other. Another way is to make a true friend your mentor (a friend who tells you all what you don’t want to hear). This is a real and long-term self-development exercise that could be supported by digital tools. An example is Pear Therapeutics which has developed the first FDA approved app for “substance use disorder”. 
  • Recommended lifestyle changes for preventing NASH for adults are (from: Diehl, Anna and Day, Christopher M.D Cause, “Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis.” N Engl J Med 2017; 377:2063-2072):
    • Lose 7 to 10% of body weight if overweight or obese
    • Increase physical activity and exercise intensity
    • Reduce saturated fats in diet
    • Stop drinking sugary beverages
    • Limit alcohol to ≤1 drink/day for women and ≤2 drinks/day for men
    • Drink two or more cups of caffeinated coffee a day (reduces fibrosis)
  • Nutrition is playing a key role in NASH prevention. Discipline in what one eats is key. Therefore, people can compile a collection of recipes for avoiding sugar, alcohol and too many calorie rich meals, thus making a big step in keeping inflammation in check. 
  • Well researched supplements: People can also complement their nutrition with well researched supplements that have the potential to mitigate and prevent inflammation. They can play a role in early onset and benign conditions. Such supplements can be developed by searching for active ingredients in nature (herbs) that aim at the same disease targets pharmaceutical companies have selected for their drug development. With a focus on “what works” (the active ingredients) and “how it works” (the mode of action) novel herbal supplements can be developed that go beyond the traditional approach in natural medicine. Nature offers a vast range of active ingredients that are anti-inflammatory and can support a multi-disciplinary program in NASH prevention. This area is quite untapped and underestimated by many in the industry.

IBD (Inflammatory Bowel Diseases)

IBD is a chronic inflammatory disease of the gastrointestinal tract has become a global disease with accelerating incidence in industrialised countries. The disease is also relapsing, meaning that patients on their way of improvement fall back into the disease stage. The two main forms of IBD are Crohn's Disease (CD) and Ulcerative Colitis (UC). Like all chronic inflammatory diseases they are complex and the actual cause is still not known. It seems to be either immune dysregulation, disturbances in the microbiota, genetic dispositions and environmental factors or a combination of them. There is a range of known disease targets which all play a role in chronic inflammation. Most of these targets are also related to other chronic inflammatory diseases like Cytokines (e.g. TNF-alpha) and various other growth factors. No matter what the cause is, people with IBD experience significant negative impacts in their business and social life. 

The prevalence of IBD is highest in Europe with 0.5% of the adult population (ca. 3million), in the USA 0.5% (1.6 million) and Asia on the rise from nearly non-existent decades ago to a visible health issue (e.g. Hong Kong from 0.1 cases per 100,000 to 3 per 100,000). The economic burden caused by the diseases grows accordingly. For a comparably small country as Australia the economic burden is ca. $3 billion, for other industrialised countries like the USA with ca. $30 billion, the costs are accordingly high. All in all, the costs per IBD patient per year are higher than for diabetes, coronary artery disease, stroke, or COPD (Economic Burden IBD, Peters.pdf).

As already mentioned, IBD are complex inflammatory diseases. There is no cure and the conventional therapy includes corticosteroids, antibiotics and antibody therapies. All therapies are known for sometimes severe side-effects and as shown above, they are very expensive.

Big pharmaceutical companies are investing heavily new IBD therapies (e.g. Pfizer, J&J, AbbVie, Takeda). The complexity of the disease and its multifactorial causes becomes clear when looking at the landscape of disease targets on the industry’s radar (a good overview on IBD disease targets, Neurath, Nature 2016).  

The natural medicine industry can play also a role, in developing new, at least complementing, therapies. Natural products have shown efficacy and less side effects (Herbal and plant therapy IBD). Especially in mild and benign cases of IBD, natural therapies can be important, given the “heavy” alternatives of pharmaceutical drugs. 

Complementing one’s nutrition with probiotics and anti-inflammatory supplements can also play role in prevention of IBD and the unavoidable exercising, which can’t be left out in any disease prevention scheme. 

COPD (Chronic Obstructive Pulmonary Disease)

COPD is a chronic inflammatory disease that affects the lung. COPD causes damage to the lungs and can't be reversed. Its main forms are emphysema and chronic bronchitis. The list of comorbid diseases is long and includes lung cancer, cardiovascular diseases and osteoporosis and depression. Patients have difficulties to breath and over time it mostly gets worse. COPD is mainly caused by smoking and then, way behind, air pollution. It is a progressive disease that affects approximately 5-10% of all adults in European countries. In the USA, 3 million people are suffering from COPD. Currently ranked 4th of the World Health Organisation’s mortality list, it will be the 3rd leading cause of death by 2030 (some say already in  2020). In Europe we see 300,000 deaths from COPD each year. The disease has a significant impact on patients’ quality of life. Still, COPD is vastly unknown (COPD explained). 

COPD (together with Asthma) medicine is seen as the least developed of all major therapeutic areas (a recent review on pharmaceutical therapies New Therapies in COPD, Gross and Barnes). The economic burden of COPD is calculated with 6% of the EU’s healthcare budget (ca. $45 million p.a.) and total cost in the USA is ca $50 billion p.a. and that does not include is the economic value of care provided by family members to patients. 

There is no cure for COPD but treatment can help and ease the physical and psychological burden of the disease. In the pharmaceutical industry GSK, AstraZeneca and AbbVie are key players in COPD R&D. Treatment very often goes along with inhalers to make breathing easier. Further care is available through oxygen therapy. The natural medicine industry has not much to offer, if anything. 

Smoker’s cough has the same symptoms as when one catches a cold. However, having COPD and catching a cold significantly intensifies the symptoms. Therefore, vaccination against influenza and pneumococcal infections and avoiding to get in contact with people with a cold are mitigating strategies. Here is an area where natural medicine can help indirectly with well researched products that support preventing to catch a cold or infections of the upper respiratory tract. 

We have observed that all pharma companies and health organisations active in COPD are promoting a lot of advice in how to deal with COPD and how still to live a good life (if the disease is not too advanced yet) e.g. Free COPD Resources, GSK and  Lung Foundation Australia Patient-support COPD  and Get-advice COPD.

Lifestyle changes are on top of the list what people can do about COPD. And this is where self-care plays a big role. Exercise is essential even when short breathness is a problem (this helps to get the lungs somehow into a rehab stage). A good support is provided through an action plan LFA COPD-action-plan (this is for health professionals but can be used individually when one is mentally strong).

However, not to start smoking or if one smokes, stop smoking are by far the best advices that one can get and one of the best goals one can have in life. Yes, this is easier said than done but when we look at the burden of disease caused by smoking and especially the growing COPD it can turn one dizzy. Maybe the boldest statement in that regard is “Telling people NOT to smoke seems to be the greatest medical contribution of the last 60 years”. Or in more detail “The harmful effect of smoking are roughly equivalent to the combined good ones of EVERY medical intervention developed since the war. (…) Getting rid of smoking provides more benefit than being able to cure people of every possible type of cancer” (from “Taking the Medicine”, Druin Burch, 2009).

As with all chronic inflammatory diseases COPD has its onset early and smoking often starts when we are teenagers. Therefore school and parents are required to act much more intensely in education and prevention of COPD. Given the support national health organisations are already providing, school and parents might be the missing link to make this all work.

In summary, where are we going with chronic inflammatory diseases? Because we human beings are very bad in preventing diseases (and other bad things) medicine development for these growing health problems will remain crucial to find therapies and new drugs. But, no matter how good the new drugs and therapies or natural products are, chronic inflammatory diseases are always connected with lifestyle and they start early in life. This clearly indicates that everybody can do a lot to prevent or mitigate these disease conditions. Therefore, multidisciplinary approaches including education have to play a much stronger role in developing and reinstating healthy lifestyles. This includes parents who have to act as role models in healthy behavior. 

Given that the pharmaceutical companies are primarily focusing on the more severe disease conditions, sometimes later in the disease development, there is a huge gap for self-care that needs to be filled systematically. Disease prevention and mitigating disease development in in its early stages with strong elements of self-care is not a question of convenience or “nice to have”, it is a must.

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