Adrenal Function and Asthma

Most people consider asthma an involuntary immune reaction to a respiratory allergen. Scientists have recently investigated asthma for its similarities to other autoimmune conditions, such as type-1diabetes. Most asthma cases are associated with lung tissue overreacting to something the respiratory system senses and responding by becoming inflamed to eliminate a pathogen. The immune response in asthma is hyper-responsive. It reacts too quickly and too often. This hyperactive immune response can eventually become chronic and lead to the development of antibodies. The inflammatory response, which starts as a reaction to a possible allergen, reacts even when no allergens exist.

Before steroid inhalers, people with asthma used to be injected with epinephrine to force an adrenal anti-inflammatory response. Then, researchers saw that the recently synthesized cortisone worked as an anti-inflammatory on eczema and dermatitis (and on any other skin eruption doctors encountered); a team of British researchers launched the first corticosteroid inhaler in 1972. Eventually, researchers realized that hydrocortisone, prednisone, and all the other recently invented steroid treatments work as anti-inflammatories because they are cortisol analogs—they do what endogenous cortisol is supposed to do naturally. Since something that worked like cortisol reduced inflammation, they wondered if the cause of asthma was low cortisol. They reasoned those steroid inhalers might be working because there wasn’t enough cortisol to begin with.

Dozens of research papers came out demonstrating a connection between maternal and early life stress and asthma development. A study of women in households with domestic violence demonstrated a 20-40% increase in asthma in women. A sustained stress reaction to maternal stress disrupts HPA, autonomic, neuroendocrine, and immune systems. Stress experienced in utero has a massive effect on childhood diseases, specifically autoimmune atopic dermatitis and asthma. Fetuses of mothers experiencing domestic may have high stress while in the womb, which then turns into a blunted cortisol response, so they are born with lower cortisol levels.

The HPA axis develops between 2 and 6 months, and the autonomic nervous system— comprising both the sympathetic and parasympathetic systems—finishes forming between 6 and 12 months. The HPA axis is the physiological regulator of stress. It becomes hyper or hyporeactive. This affects how adrenal function modulates the immune system. Children of parents experiencing stress are more likely to have respiratory infections. Children born to mothers often have asthma and a disordered immune response, predisposing them to eczema and other autoimmune conditions.

Unfortunately, maternal stress is a huge factor. Maternal anxiety raises cortisol levels in the fetus through amniotic fluid, and cortisol passes to the fetus through the placenta, affecting the biochemical development of the HPA axis. Long-term anxiety, antenatal and postnatal, is associated with higher rates of asthma in children. Antenatal anxiety was also associated with higher postnatal anxiety. These children develop hypersensitivity to stress but have a blunted cortisol response. The lowered endogenous cortisol compromises the body’s natural protection against airway inflammation. It’s an immune system gone haywire.

Some substances can raise cortisol levels and, therefore, cause indirect stress, such as drugs, smoking, alcohol, malnourishment, and a high-carbohydrate diet. But factors such as discrimination, financial strain, job strain, food insecurity, unwanted pregnancy, and maternal exposure to partner violence cause psychosocial stress that is more prevalently associated with risks to fetal cortisol levels, with maternal partner violence being the most destructive. A woman who has chosen to have a child will suffer less stress and bear a healthier child.

All people with asthma have lower cortisol rates than controls. They also have a dysregulated diurnal rhythm of cortisol excretion, with the peak occurring in the late afternoon instead of the morning. They suffer more from nocturnal asthma. Nighttime cortisol rates are supposed to be lowest during the night, but many people with asthma have abnormally low levels at this time. Children with low cortisol have lower FEV and forced expiratory volume, meaning they cannot exhale properly, which will also cause lower carbon dioxide levels (but then eventually high carbon dioxide levels) which is why my grandmother told me to breathe into a paper bag when I suddenly couldn’t breathe air the time my mother remarried, went on her honeymoon, and left me with my grandmother. Children taken from their parents are also at risk for asthma. Higher cortisol levels mean better lung function. This is why those steroid inhalers work, providing the cortisol people with asthma aren’t producing correctly. Not because of any pathology but because their HPA axis signaling has been altered due to stress.

There is a happy ending to this story. Researchers explored how environmental enrichment, including social, cognitive, physical, sensory, and food enrichment, reversed early stress hypersensitivity and immune hyper-reactivity. The symptoms of children of mothers who had suffered antenatal and postnatal stress improved or disappeared when maternal stress was removed and experienced, and the children received sensitive caregiving with rich maternal-child interaction. The study also demonstrated that removing factors causing stress removal and increasing quality of life undid the effects of prenatal stress and reprogrammed the HPA axis response to stress, normalizing cortisol levels and effectively reducing the rate of asthma in children.