À bout de souffle

It’s getting harder to breathe.

Two of the main degenerative conditions which make breathing difficult, namely chronic obstructive lung disease (COPD) and pulmonary hypertension (PH), appear to be trending upwards (1, 2), and are certainly becoming an increasing global burden (1-3).

If you have COPD you are more likely to acquire PH (4), so the two conditions may co-exist in the same unhappy patient; but pulmonary hypertension can and often does arise in the absence of COPD. The various sub-types of PH include pulmonary artery hypertension (PAH), a condition which originates in pulmonary arterial inflammation, re-modelling and increased resistance to blood flow. Other types of PH with different causes will, if untreated, eventually create similar vascular changes and arrive at broadly similar clinical endpoints.

This post omits any discussion of PH secondary to sleep apnea, toxins, drugs or other risk factors where the primary cause can be isolated and, ideally, treated.

The main risk factors for COPD are long-term exposure to inhaled irritants like cigarette smoke, air pollution, occupational dusts and fumes – and a poor diet (5). Genetic risk factors are known, but less prevalent. In PH the risk factors other than COPD include obesity, inflammatory autoimmune disorders such as lupus, rheumatoid arthritis and Sjogren’s, a few genetic links, methamphetamine or cocaine abuse – and a poor diet (6).

Conversely, the available evidence indicates that a diet rich in fruits, vegetables, fish, olives and whole grains, such as the traditional Mediterranean diet, is protective against both COPD (7) and, indirectly, PAH and PH in general (8-10).

Today’s industrial diet is very far from the Mediterranean diet (or any traditional diet), and kills via the usual suspects: dysbiosis, chronic inflammation, Type B malnutrition and glycemic imbalance. A fifth pathogenic mechanism involves an abnormal dietary ratio of the electrolytes sodium, potassium and magnesium. All of these mechanisms feed directly into the pulmonary pathologies described above.

1. Dysbiosis

Today’s industrial low-fiber diet inevitably causes colonic dysbiosis, which has recently been shown to be associated with an altered pulmonary microbiota in COPD (11-13). The dysbiotic pulmonary microbiota contributes to chronic inflammation and further damage in the lungs (14-16); see below. This is a bi-directional relationship, in that lung disease appears to raise the risk of GI disorder, likely via hypoxia and/or immune cross-talk. This is termed the gut / lung axis or theory (10, 17-19, 22, 23). Colonic dysbiosis is also strongly linked to an increased risk of PAH (20-22), primarily via endotoxemia (24, 25).

       2. Chronic inflammation

COPD (26, 27), PH (28) and PAH (29, 30) are all associated with and driven by systemic inflammation, and present with increased levels of inflammatory markers. Colonic dysbiosis adds a chronic systemic inflammatory component (31), so comes in here too. In COPD, chronic inflammatory stress drives the progressive destruction of the alveoli and bronchioles. This same chronic inflammation increases the risk of PAH, and most other forms of vascular and cardiovascular disease (32). In PH and especially in PAH, chronic inflammation drives the progressive thickening of the walls of the pulmonary arteries that raises blood pressure in the pulmonary circuit (33-36).

The well-established link between left-sided cardiovascular disease and PH and COPD (31) is usually explained by mechanical factors, ie increased back pressure in the pulmonary circuit. However, given that essential (systemic) hypertension, arterial re-modelling and atheroma are driven by chronic inflammation (37), and that pulmonary arterial hypertension, re-modelling and atheroma are all part of PAH (ie 30) and the first two of these three occur in PH also (38), it seems equally likely that these pathologies in the left and right sides of the circulation are commonly associated because they also share a common aetiology.

The anti-inflammatory Mediterranean diet protects against CVD and COPD (7-10), but I am not aware of any studies showing that it directly reduces the risk of PH and PAH. The fact that most medical authorities recommend PAH patients to follow a heart-healthy diet, however, hints that such a diet might be preventative here also.

      3. Type B malnutrition

Micronutrient deficiencies involving vitamins A, B12, folic acid, C, D, and E, and the minerals magnesium, selenium, and zinc, are common in individuals with COPD and are linked to poorer lung function and more frequent exacerbations (ie 39). This is likely a reflection of impaired antioxidant enzyme capacity, which directly increases chronic inflammatory stress (40).

      4. Glycemic Imbalance

Loss of glycemic control is a risk factor for and is associated with worse outcomes in COPD (41, 42), PH (43) and PAH (44-46). It amplifies oxidative and inflammatory stress (47), increasing local tissue damage and at the same time impairing repair mechanisms (47).

      5. Electrolyte Imbalance

Excess sodium exacerbates PH, PAH (48) and COPD (49) via a deeply negative interaction. Increased plasma volume drives pulmonary congestion, and increased smooth muscle tone worsens pre-existing airflow restriction (50-52).

The modern industrial diet damages our physiological systems via all of the above mechanisms, and is the most important driver of today’s multiple pandemics of chronic non-communicable disease. Why would one expect chronic lung disease to be any different? It’s not just about smoking … in fact, the deleterious effects of tobacco can be substantially modified by dietary factors.

In one 12-year study, male smokers with high Mediterranean diet intake were roughly 50% less likely to develop COPD than those with low intake (53). An earlier observational study by the same scientists had found that women eating the Western diet were about 4 times more likely to develop it (54). These findings emphasise once again how vulnerable industrial foods make us (55), and it seems obvious that a return to more traditional eating habits would produce significant improvements at the public health level. It should help affected individuals also.

But we can do more. We can use the Health Protocol to further reduce chronic inflammatory stress, and remove dysbiosis and endotoxemia from the equation.

Driving the omega 6:3 ratio down and the 3-index up, damps and inhibits the chronic inflammatory cascade. Fish oil combined with the correct chaperones will do this (56).

Omega-3 conjugates offer additional specific help with PAH (57), which makes this approach even more interesting.

Blended prebiotic fibers restore a pre-transitional microbiome, and the endotoxemia associated with the modern diet (58). A broad-spectrum micro- and phyto-nutrient support program will alleviate Type B malnutrition, a lower-carb and higher exercise lifestyle reduces or removes the glycemic overload component, and table salt can be replaced with PanSalt.

Given that the alveoli are exposed to a high partial pressure of oxygen, lung health programs should also include appropriate antioxidant support. The relevant small molecules include ascorbate, beta carotene, alpha-tocopherol and perhaps more so the tocotrienols (ie 59); combined with the trace elements selenium, copper, zinc, manganese, which provide co-factors for glutathione peroxidase and the catalases.

NADPH plays a key role in the redox enzyme cascade, making mitochondrial health fundamentally important. This is a good reason to stock up on prebiotic fiber, which reduces the kynurenine / IPA ratio (60, 61) and enhances mitochondrial function (62).

Due precisely to the high ppO2, smokers should avoid beta carotene supplements and unchaperoned fish oil.

An anti-inflammatory, eubiotic and micronutrient-dense diet will likely be protective, and the HP will add to that; but what if alveolar damage has already occurred? Can these delicate structures be repaired?

The fact that alveoli can be destroyed by smoking, toxins, bacterial and viral pulmonary infection, excessive coughing, even strenuous exercise, makes it hard to believe that there aren’t substantial repair mechanisms.

The walls of the alveoli where gas exchange occurs consist of a single layer of cells, and are as thin as 0.2 micrometers. This enables rapid diffusion of O2 and CO2, and it also confers extreme fragility. It is therefore inherently likely that alveoli continually break down and are repaired / regenerated.

The respiratory system does indeed have an extensive ability to respond to injury and regenerate dead or damaged cells. To this end the lungs are stocked with various progenitor cells, which are half-way between ordinary cells and stem cells and which are ready to rush into the breach to promote repairs when and where needed (63).

Timing is critical because the extent of regeneration depends on the type, severity and duration of the injury. After minor to moderate acute and semi-acute damage, the lung can heal through the activation of progenitor cells and the proliferation of existing cells to restore structure and function (63, 64); and will likely do so most successfully in metabolically supported individuals.

The lungs can heal readily after acute injury such as bronchitis, but it is generally believed that healing cannot occur after chronic injury (ie long-term smoking) and subsequent scarring, and that emphysema or COPD would always progress. This is what clinicians experience in a post-transitional landscape, where the COPD patient is suffering from chronic inflammatory, glycative and other stresses, dysbiosis and Type B malnutrition. But perhaps it is not intrinsic.

I suspect the reason why clinicians do not see evidence of healing in conditions such as COPD is that any potential for regeneration is swamped by the metabolic chaos created by the modern diet and lifestyle. By using pharmaconutrition to provide a supportive milieu interieur, the lungs’ built-in ability to repair themselves should be enhanced and revealed. Genetic organisational instructions might still be operative even in chronic cases, given the right environment.

In the typical patient who is exposed to ongoing harm (ie smoking or vaping) and is also nutritionally compromised, the degree of damage will reach a point where regenerative functions can no longer prevail. Fibrosis and progressive loss of lung function ensue, unless acute illness intervenes. Appropriate nutritional support might be helpful, however, even in more advanced and more fibrotic cases.

This progressive loss of lung function is one of the more difficult and distressing ways of dying, and is best avoided. Preventive pharmaconutrition will help to prevent progression, or at least slow it.

Keep breathing (65).

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