For at least 2 decades, it has been widely recognised that obesity increases asthma incidence, impairs asthma control, diminishes response to therapy with inhaled corticosteroids (ICS), and increases the chances of an asthma exacerbation. Abdominal obesity appears the most important risk factor.
Obesity stimulates bronchial hyperresponsiveness and leads to a steeper loss of lung function. “While there are varying degrees of strength and consistency in these associations, taken together, they strongly suggest that metabolic dysregulation/obesity can worsen airway function and adversely affect the health of patients with asthma,” Prof. Fernando Holguin (University of Colorado Asthma Research and Education, CO, USA) explained .
In the longitudinal CARDIA cohort, 4,619 participants were followed for 25 years – 602 developed asthma . Results indicated that metabolic syndrome predicted incident asthma among women but not men. BMI had a similar predictive association among women but not men. However, in the adjusted model only BMI was significantly associated with future asthma. “BMI is a more significant parameter than metabolic syndrome,” Prof. Holguin concluded. In a French study including 121,965 men and women examined between 1999 and 2006, a positive independent relationship between lung function impairment and metabolic syndrome in both sexes was found .
Abdominal obesity in women: 50% elevated risk to develop new-onset asthma
In CARDIA, abdominal obesity was the most important risk factor for loss of lung function in both men and women for FEV1 (OR 1.94; 95% CI 1.80–2.09) and FVC below the lower limit of normal (OR 2.11; 95% CI 1.95–2.29). Another cohort study emphasised the importance of abdominal obesity: in the Nord-Trondelag Health study, 23,191 participants who were asthma-free at baseline were followed for 11 years . During this period, self-reported new-onset cases of asthma were assessed. General obesity was a risk factor for asthma in women and men. In women, after additional adjustment for BMI, abdominal obesity (waist circumference of ≥88 cm) remained a risk factor and was associated with a 50% higher risk to develop asthma . Therefore, Prof. Holguin pointed out that both measures of BMI and waist circumference in women may be a superior clinical assessment for asthma risk than any measure alone.
Metabolic factors are more important than weight loss
An interesting insight on the influence of metabolic factors on asthma development was given by a study on the impact of bariatric surgery on asthma control. Among 2,458 participants of the multi-centre LABS study, change in asthma control was assessed in the 555 participants with an asthma diagnosis . Of these, 78% (n=433) met criteria of metabolic syndrome at baseline. After the procedure, most patients lost weight. The proportion of participants with metabolic syndrome dropped from 78% at baseline to 36% at 1 year of follow-up, and subsequently continued to slowly drop to 30% by 60 months. “Looking at the group of patients that continued to have metabolic syndrome despite weight loss, those patients had a much higher hazard ratio of about 90% to lose asthma control. This is quite striking and suggests that not only one has to lose weight, but one also has to improve some of these metabolic factors,” concluded Prof. Holguin. When the researchers assessed the association between the individual components of metabolic syndrome and the risk of uncontrolled asthma, again central obesity turned out to be most important. These patients had a more than 2.5 times elevated relative risk to lose asthma control . In a retrospective cohort of US obese adults with asthma, prediabetes and diabetes were associated with higher rates of asthma exacerbations: compared with individuals with normal HbA1c, those in the prediabetes range had a 27% higher rate (95% CI 5–52%), and those in the diabetes range had a 33% higher rate (95% CI 2–73%) of exacerbations .
Diabetes therapeutics can have beneficial effects
Interestingly, therapy of type 2 diabetes can influence the risk of asthma exacerbations. In a study published recently, asthma exacerbations in patients with type 2 diabetes and asthma treated with glucagon-like peptide-1 receptor agonists (GLP-1R) were compared with patients with type 2 diabetes receiving other antidiabetic medications . Patients treated with a GLP-1R had a significantly lower risk of asthma exacerbations within 6 months of drug initiation compared with patients in all comparator groups. “This suggests some protective effect of GLP-1R agonists, which is worth exploring,” Prof. Holguin explained. Another antidiabetic that might have a favourable influence on the risk of asthma exacerbations is metformin. In a claims-based cohort study including 23,920 individuals with asthma and diabetes, therapy with metformin was associated with lower hazard of asthma exacerbations, but there were no differences in the use of corticosteroids in patients .
One of the mechanisms that could play a role in patients with asthma and metabolic risk factors is a high IL-6 concentration. In a study, exacerbation prone asthma was characterised by lower FEV1 and a higher prevalence of obesity. High-plasma IL-6 concentrations occurred in these patients, and there was an increased risk of asthma exacerbation of 9% for each 1-pg/μL increase in baseline IL-6 level .
Taken together, multiple mechanisms lay behind the detrimental effects of metabolic dysfunction on asthma and other respiratory diseases .
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