Different phenotypes drive early, late onset asthma

Key takeaways:

• Patients with early onset asthma (EOA) had significantly lower values of FEV1 and forced vital capacity (FVC) than patients with late onset asthma (LOA).
• Rhinitis was more frequent in EOA and associated with uncontrolled asthma, whereas it was associated with more controlled asthma and higher FEV1/FVC in LOA.
• Obesity was associated with uncontrolled asthma, reduced FEV1/FVC and blood neutrophils in LOA but not in EOA.

Early onset persistent asthma and late onset asthma have distinct phenotypes with different features and comorbidities impacting disease control, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.

These differences could drive personalized approaches to care, Martina Turrin, MD, of the department of cardiac, thoracic and vascular sciences and public health at the University of Padova and Padova City Hospital in Padova, Italy, and colleagues wrote in the study.

The researchers examined 175 adults treated for asthma at the Padova University Hospital Respiratory Disease Clinic between January 2018 and January 2020. These patients had a mean age of 57.5 ± 17.1 years, and 59% were women.

Based on Global Initiative for Asthma guidelines, 20% of patients were in steps 1 or 2 of treatment, 70.3% were in step 3 and 9% were in steps 4 or 5. Less than 1% of patients were not on therapy. All of the steps 1 and 2 patients and 46% of the step 3 patients had controlled disease, whereas 98% of patients in steps 4 and 5 were poorly controlled.

Also, 62.8% of the full cohort had allergic rhinitis, 60.5% had gastroesophageal reflux disease (GERD), 21.7% had obesity, 6.2% had a history of bronchiectasis and 25.1% had cardiovascular comorbidities.

Additionally, 44% of these patients had early onset asthma (EOA), defined as initiation of disease before age 12 years, and 56% had late onset asthma (LOA), or disease that began after age 40 years.

The patients with EOA had values of FEV1 and forced vital capacity (FVC) that were significantly lower than patients with LOA, even when they were within the normal range, which the researchers said suggested sub-maximal development of lung volume.

The researchers additionally found that 75.3% of the patients with EOA and 53% of those with LOA had rhinitis (P = .002). Among the patients with EOA, 95% of those with uncontrolled asthma and 47% of those with controlled disease had rhinitis.

Further, the patients with EOA and rhinitis had higher total serum IgE levels, higher blood eosinophil counts, lower FEV1 values and lower FEV1/FVC values than the patients who had EOA but no rhinitis.

The researchers found a significant correlation between serum IgE and blood eosinophils levels (Spearman correlation coefficient = 0.42; P < .001) and a negative correlation between FVC₁/FVC ratio and IgE (Spearman correlation coefficient = –0.35; P = .002) and eosinophils (Spearman correlation coefficient = –0.40; P < .001) among the patients with EOA as well. The patients with LOA did not have any of these correlations.

However, rhinitis did have an opposite association between airway function and disease control among patients with LOA, as those with concomitant rhinitis had significantly better airway function than those without it.

The researchers also found that 78% of those patients with LOA and uncontrolled asthma had no rhinitis, compared with 28% of those with LOA and controlled asthma. Similarly, there was no association between rhinitis and increased IgE levels or eosinophil count among these patients.

With 53.2% of patients with EOA and 66.3% of those with LOA reporting GERD, the researchers found no significant difference between the groups, nor did the researchers observe any relation between GERD and severity of disease, respiratory function, or IgE and eosinophil count. But most of these patients were on therapy for GERD, the researchers cautioned, which could account for these results.

Obesity percentages were similar for the EOA (22.3%) and LOA (21.4%) groups and 21.7% for the entire cohort. The researchers did not find any relationship between obesity and disease control in the EOA groups, with the same prevalence among patients with controlled and uncontrolled asthma.

However, the researchers found a significant association in the patients with LOA, with 35% of patients with uncontrolled asthma and 12% of those with controlled asthma also having obesity.

Compared with patients with EOA and normal weight, patients with EOA and obesity had impaired respiratory function characterized by reduced FEV1 and FVC, although their FEV1/FVC ratio was normal.

Patients with LOA and obesity experienced an obstructive pattern with reductions in FEV1, FEV1/FVC and forced expiratory flow at 25% to 75% of forced vital capacity, although there was no difference in FVC.

Plus, the patients with LOA and obesity had a neutrophilic pattern of inflammation that the patients with EOA and obesity did not have. The researchers said that this suggests that obesity adds an inflammatory contribution to late onset asthma. There were no differences between the groups in eosinophils.

The researchers additionally found that 2.6% of the patients with EOA and 9.1% of those with LOA had bronchiectasis, which they did not consider a significant difference, although they cautioned that the small number of patients with this diagnosis limited the power of this analysis.

Similarly, there were no differences between the EOA and LOA groups in terms of cardiovascular comorbidities, which affected 25.1% of the whole population. There were no differences in disease course between men and women patients either.

Among the EOA patients, rhinitis was the most important risk factor associated with poor control. But among the LOA patients, there was an association between rhinitis and better control. Also in the LOA group, obesity was most closely associated with poor control. Both groups experienced better control with higher FEV1/FVC values.

Based on these findings, the researchers concluded that EOA and LOA involve two different phenotypes with distinct and functional characteristics. Comorbidities have specific and different impacts in these groups as well.

By accounting for these differences, the researchers said, clinicians may be able to craft more personalized treatment plans that focus on individual characteristics while preventing the need to escalate therapy.