Asthma and metabolic syndrome – along with obesity – are associated with a multitude of health problems – but even a change as minor as a 5% weight reduction can help
This 36-year-old gentleman attended the hospital over the last 12 months with poorly controlled asthma, which proved resistant to treatment. His asthma symptoms also suggested the presence of metabolic syndrome. Ben had been working hard from home during the lockdown. As his workload increased, he found it impossible to balance work and family life, finding it difficult to support his children with home-schooling, which resulted in marital conflict.
With the increasing pressure and stress, Ben gained nearly two stone in weight. He attributed this to his consumption of energy-dense snack foods, an increase in alcohol consumption as a coping mechanism, and a lack of physical activity whilst working from home.
Ben attended the hospital more frequently due to the deterioration in his asthma control. He went from having infrequent symptoms, requiring an occasional reliever (bronchodilator inhaler), to needing it on a daily basis. His doctors informed him that he might need to go on an oral corticosteroid. This did not appeal to Ben, and hence he reached out for new ideas.
Oral steroids – “a huge and scary jump”
Ben attended the Vitality Clinic with daily symptoms requiring a short-acting reliever (Ventolin.) His symptoms woke him up at least once a week. Ben brought a summary of his medical records, with an FEV1 vital capacity of 72% of predicted. Post inhaler FEV1 showed a 10% improvement. This classified Ben with moderately persistent asthma.
He was on step 3 treatment, including inhaled corticosteroid and inhaled long-acting bronchodilator (Salmeterol) twice daily. Ben felt that going on oral corticosteroid was a huge and scary jump from step 3 to step 6 on the treatment ladder. This was enough to make Ben seek more help.
During the Vitality Clinic assessment, we discovered that Ben had all of the metabolic syndrome components, with central obesity – waist size 42 inches, hip size 40.5 inches and WHR 1.04 – HDL (the good guy) low at 0.92, triglyceride high at 2.3, blood pressure 135/85, and prediabetic blood sugar at 6.4. Ben also recorded a reduced peak flow of around 280.
Obesity is a well-recognised risk factor for asthma, associated with poor response to treatment and more severe and refractory disease. Other components of the metabolic syndrome, including high insulin levels, abnormal lipid profile, and hypertension, also play a role in the causation and progression of asthma. As with metabolic syndrome, interventions aimed at reducing weight and introducing a healthy diet produce significant benefits for asthmatic patients.
Looking from the other direction, studies have confirmed that asthmatics are at a greater risk of having metabolic syndrome compared with non-asthmatic controls. Other studies have demonstrated that optimal asthma control is lower in obese asthmatics than in those with normal weight.
Do you have asthma?
The main symptoms of asthma are coughing, wheezing, chest tightness, and breathing difficulty. Symptoms are usually intermittent or persistent, can vary in severity and frequency, according to the criteria below:
Asthma and metabolic syndrome
We know that the comorbidity of asthma and metabolic syndrome is always associated with poorly controlled asthma, often refractory to standard medical therapy when the two conditions co-exist; there a great chance of improving asthma symptoms if we can help the patient to lose weight.
One large study of 23,000 adults reported that a person with metabolic syndrome has a more than 50% higher risk of asthma during 11 years of follow-up.
Most research has focused on belly fat as a source of inflammation, worsening asthma control, and treatment outcomes. In other words, the adipose tissue (belly fat) is not just stored fat but active endocrine tissue that produces hormones and inflammatory cytokines (chemical messengers) to escalate inflammation all over the body. The asthmatic chest is no exception.
Metabolic syndrome can also deprive you of the body’s natural anti-inflammatory mechanism, which is designed to quench inflammation in various parts of your body. The best example is adiponectin, which protects the bronchial epithelium involved in the pathogenesis of asthma. It is a potent anti-inflammatory hormone that has a specific power to inhibit eosinophil, the type of white blood cell that, when activated, triggers asthma attacks. With obesity, diabetes, and metabolic syndrome, your adiponectin levels plummet.
Systemic inflammation may also make it possible for other components of the metabolic syndrome to show up. It is also known to drive insulin resistance, which can result in endothelial (the blood vessel lining) cell dysfunction, an important underlying cause of high blood pressure.
Pro-inflammatory cytokines, which lead to the development of metabolic syndrome, can also contribute to asthma. IL-6, tumour necrosis factor-alpha (TNF-alpha), and leptin have been found in obese asthmatics. IL-6, a biomarker of systemic inflammation, is associated with hypertension and diabetes and also with severe asthma in obese and non-obese patients.
Lower levels of antioxidants have been reported in asthmatics and the obese, contributing to an increase in systemic oxidative stress, contributing further to the pathological imbalance.
High oxidative stress with high reactive oxygen species induces functional changes in the respiratory airways and can increase asthma severity. The renin-angiotensin-aldosterone system was found to be a potent inducer of oxidative stress. The final product of the above system, angiotensin II, plays a role in determining bronchial hyperresponsiveness.
“Stop eating!” shouts leptin
Leptin, another hormone, guides your appetite by telling you to stop eating when a certain threshold is reached. However, most people with obesity and metabolic syndrome have a very high level of leptin, so the hypothalamus (appetite centre) loses its sensitivity to this hormone (leptin resistance.) This clears the way for leptin to increase secretion of pro-inflammatory cytokines, which include TNF alpha, interleukin 6 (IL-6), and interlocking 12 (IL-12), to exacerbate the asthma attack. As well as enhancing systemic inflammation, leptin may lead to a decline in lung function.
Abnormal lipid profile in the metabolic syndrome includes high triglyceride and low HDL (the good guy), which plays a role in the pathogenesis of asthma. HDL (the protector) was found to promote the production of the surfactant, an important substance produced by the pulmonary (lung) cells to keep the lung inflated.
Plummeting HDL levels in metabolic syndrome result in the decline of lung function in asthmatics. One study found that lower levels of HDL increase the risk of asthma in adolescents. Another study reported high triglyceride and low HDL were associated with more wheezing in asthma patients, supporting the view that these lipid components are markers of inflammation.
The metabolic syndrome usually presents with high levels of insulin, as the pancreas continues to produce increasing amounts because of the loss of insulin sensitivity, a clinical scenario recognised as “insulin resistance,” which plays a central role in the metabolic syndrome. There is significant evidence in medical literature to indicate that insulin excess may directly alter lung function.
Insulin growth factor one (IGF-1) was linked to lung development and function. There is evidence that hyperinsulinemia (high insulin levels) may lead to the development of asthma in the first place.
Hyperinsulinemia interferes with the anti-inflammatory effect of insulin and is also associated with muscle weakness, including the respiratory muscles. This is because it reduces glucose utilisation and induces abnormal fat metabolism in the muscles, which may impair energy production in the mitochondria.
Wheezing in school-age children
Clinical studies showed higher and faster weight gains were associated with the risk of wheezing and asthma in preschool and school age children. The prevalence of asthma increases in direct relation to rises in body mass index. And the severe form of allergic eosinophilic asthma (type II asthma) has been associated with obesity. The presence of obesity can also predict bronchial hyperresponsiveness in asthmatics.
Studies reported insulin resistance, the hallmark of metabolic syndrome, as a risk factor for lower lung function or accelerated lung function decline. Direct exposure of the airways to insulin can result in bronchial hyperresponsiveness.
The previous practice of administering insulin in emergency situations through inhalation via the lung (now discontinued) resulted in coughs and dyspnoea, along with a reduction in lung function and impaired gas exchange through the lung membrane. Insulin resistance may increase bronchial activity.
Both visceral fat accumulation and weight gain have been associated with the development of asthma in type two diabetic adults. Dyslipidaemia (disturbance in the concentration of lipids in the blood) has been reported as a risk factor for impaired lung function and accelerated lung function decline.
One study reported that lower doses of inhaled corticosteroids were protective, while the opposite is true for higher doses. This may suggest that higher doses of steroids may set the scene for metabolic syndrome.
Beyond obesity, both dyslipidemia and hyperinsulinemia can influence both the innate and the adaptive defence immune mechanism in the respiratory tract, with pro-inflammatory cytokine and chemokine production, to increase bronchial tone, leading to bronchospasm (narrowness of the bronchial tree,) wheezing, and asthma symptoms.
Amino acids have an antioxidant function, with glycine, glutamine, and cysteine contributing to the formation of glutathione, the master antioxidant. These amino acids can be oxidised due to the high levels of oxidative stress associated with metabolic syndrome. Depleting the body of the master antioxidant, glutathione, which is necessary to lower oxidative stress, removes its ability to prevent asthma attacks or lower its severity.
Asthma attacks lower the body’s oxygenation, shifting energy production from the highly sophisticated mitochondria (energy plants) to the primitive way of making energy by glucose fermentation (glycolysis) in the cytoplasm. This method is prevalent in the primitive life of unicellular organisms such as bacteria and amoeba. But glycolysis can also be found in obese people: having the two conditions together in one person can result in severe fatigue and lethargy.
Control your asthma and improve the quality of your life
Obesity and metabolic syndrome are well-recognised risk factors for the development of asthma and are associated with severe refractory disease and poor response to treatment.
In treating asthma, we usually work with the respiratory team to reduce the impact of metabolic syndrome, aiming to prevent or reduce the severity of asthma. Identifying important factors that contribute to the pathogenesis of the two conditions will help to define a personalised action plan designed just for you.
An improvement in quality of life in obese asthmatic patients is most often achieved through weight loss, and even a 5 to 10% reduction can produce significant improvements in asthma control.
A diet high in sugar, refined carbohydrates, processed meat, fatty, and fried food, low in fibre is associated with low lung function and increased respiratory symptoms, even in people with normal BMI. A diet high in fibre feeds your gut microbiome population, which produces short-chain fatty acids with a positive impact on airway inflammation.
A diet high in fruits and vegetables or the Mediterranean diet has been associated with improved asthma control and quality of life among asthmatics.
Physical exercise also improves the symptoms of asthma and facilitates asthmatic control. Another potential approach is to modify the microbiome to prevent and treat asthma. Studies noticed changes in the microbiome as early signs in the development of asthma.
So, my friends, asthma can be suggestive of the presence of metabolic syndrome, and its issues are exacerbated by obesity. The solution, as always, lies around a transition towards better life choices in the areas of diet, exercise and stress reduction! Please do share your thoughts and questions by commenting on this piece, and do subscribe to the newsletter so that you don’t miss further vital information. Thank you!
Asthma and Metabolic syndrome: current knowledge and future prospective
The relationship between Metabolic syndrome and asthma in the elderly
Metabolic dysfunction and asthma: current perspectives
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