Sex, obesity, and immune disturbances inform severe asthma phenotype in later life
medwireNews: With advancing age, asthma becomes more prevalent in women than men and is associated with obesity, greater airflow limitation, and lower markers of T-helper cell type 2 (Th2) inflammation, study findings show.
The results demonstrate significant differences in the phenotypic features of severe and nonsevere asthma between children and adults, say the Severe Asthma Research Program (SARP) III investigators.
They looked at the mechanisms of asthma in 188 children (younger than 18 years) and 526 adults, of whom 111 and 313, respectively, had severe disease.
Among the children with asthma, who were predominantly male, those with severe asthma had more symptoms, more historical exacerbations, greater use of medication, and a higher degree of pre-treatment airflow limitation than those with nonsevere asthma. However, bodyweight, inflammatory markers, and the degree of allergen sensitization did not differ according to asthma severity.
At enrolment, there were more adults than children with severe asthma, with a peak occurring among those aged 50 and 55 years, while the numbers with nonsevere asthma remained stable across childhood to adulthood. Irrespective of severity, there was a significantly higher proportion of females and a higher propensity for obesity among adults than children (both p<0.0001).
The researchers, led by W Gerald Teague (University of Virginia School of Medicine, Charlottesville, USA), suggest that the reversal of the proportion of males to females after adolescence could be due to the potential deleterious effects of estrogen and progesterone on lung function and beta adrenergic receptor function or a protective effect of testosterone.
And the nearly twofold increase in obesity among adults, at 62% in severe and 45% in nonsevere asthma patients versus a respective 38% and 30% in children, provides support for obesity being “at least as important as an asthma risk factor as the metabolic syndrome,” says the team.
Lung function was more heterogeneous with advancing age. Both the pre- and post-bronchodilator ratio of forced expired volume in 1 second (FEV1) to forced vital capacity (FVC) % predicted were significantly lower (p<0.05) as age increased.
But while the percentage of patients below the lower limit of normal for pre-bronchodilator FEV1/FVC did not change significantly with age, those below this level for post-bronchodilator FEV1/FVC increased significantly (p<0.0001) with older age, from around 18% in children to 22% and 45% in middle-aged adults with nonsevere and severe asthma, respectively.
Absolute bronchodilator response fell significantly (p<0.0001) with advancing age and was the only element of lung function to be significantly (p=0.03) affected by the interaction of age and asthma severity.
“Differences in lung function with age were highly discordant with age-related differences in markers of Th2 inflammation, which improved as lung function deteriorated,” the researchers point out in the Journal of Allergy and Clinical Immunology: In Practice.
“This discordance is the bias for our speculation that alternate mechanisms, supplemental to Th2 inflammation, may favour the progression of airflow limitation with age.”
There were a further two outcomes significantly affected by the interaction of age and asthma severity. The first was prevalence of sensitization to four or more allergens, which decreased significantly (p<0.0001) with age and particularly in those with severe asthma (p=0.03). The second was exhaled fraction expired nitric oxide (FeNO) titers, which declined with age in all adults, but while exhaled NO levels were relatively consistent with age in those with severe asthma, FeNO declined sharply from 20 to 50 years in adults with nonsevere asthma.
Although not differentiated by asthma severity in adults, the team comments on the significantly higher prevalence of peripheral blood eosinophilia in children compared with adults. It fell sharply from childhood to middle age before reaching a plateau and rising again from late middle age onwards.
This effect of age on blood eosinophilia is strikingly different to that on FeNO, they note, and suggests different governing factors.
The team therefore concludes: “[G]ender effects, obesity, and novel immune perturbations that occur more commonly in middle age inform the severe asthma phenotype.”
By Lucy Piper
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