Phenotypes vary among patients with asthma, obesity

Key takeaways:

• Some patients with asthma and obesity experience derangements in peripheral airways that worsen with methacholine.
• People with obesity may experience these abnormalities regardless of their asthma status.

Using oscillometry testing, physicians may identify patients with asthma and obesity who have a phenotype that may be related to worse symptoms and more severe disease, according to a study published in CHEST.

This testing may identify patients with obesity who have subclinical abnormalities without any clinically diagnosed lung disease as well, Anne E. Dixon, MA, BM, BCh, director of pulmonary and critical care medicine, department of medicine, Larner College of Medicine, and colleagues wrote.

“We realized that many people with obesity and asthma can have fairly normal lung function when measured by conventional lung function testing (spirometry), but have very significant symptoms of shortness of breath,” Dixon told Healio.

Anne E. Dixon

“We thought this might be because spirometry measures large airway function well but is not very sensitive to abnormalities in the small airways,” she continued.

The study involved 53 patients with class III obesity who were being evaluated for bariatric surgery at the University of Vermont Medical Center, including 31 with asthma (23 women; aged 43.9 years ± 11.8; BMI = 47.5 kg/m² ± 81 kg/m²) and 22 controls with no lung disease (18 women; aged 39.9 years ± 11.1; BMI = 46.7 kg/m² ± 6.6 kg/m²).

“There are some people with obesity and asthma that have very significant dysfunction of their small airways, and this seems to be associated with worse asthma,” Dixon said. “Spirometry did not reveal very significant abnormalities.”

Compared with the control patients, the patients with asthma had slightly higher serum IgE and had smoked more often. They also had lower FEV₁, forced vital capacity (FVC), FEV₁/FVC, reactance at 5 Hz measured by oscillometry (X₅), and lower expiratory reserve volume, as well as higher residual volume, difference between resistance at 5 Hz and 19 Hz (R_5-10) and area under the reactance curve (AX).

After a methacholine aerosol challenge, the patients with asthma had greater decrements in FEV₁ and FVC than the control patients. They also responded at lower doses and had greater absolute magnitudes of R₅, R_5-19, X₅ and AX in addition to a lower peak dose of methacholine than the control group.

The percent change in X₅ was the only variable that was greater among the patients with asthma compared with the control patients, with 14 of 22 of the controls reporting greater than 50% changes in R₅ and/or X₅ at 16 mg/mL of methacholine.

There were no differences in the baseline characteristics between the control patients who did and did not have any response at 16 mg/mL of methacholine, although the patients who had an oscillometry response had a numerically higher BMI and waist circumference as well, in addition to greater spirometry response.

Due to these findings, the researchers said, the distal lung dysfunction that a high proportion of people with class III obesity experience in response to moderate doses of methacholine may represent subclinical airway reactivity.

The researchers also characterized the correlation between percent change in FEV₁ and FVC among the patients with asthma and the controls as strong, although they added that the correlation between percent change in FEV₁ and percent change in AX and A₅ was good among the control patients but not in the patients with asthma.

Additionally, the researchers divided the patients with asthma into those with a low peak bronchoconstriction reactance or AX of less than 100 cm H₂O/L and those with a high peak bronchoconstriction reactance or AX of 100 cm H₂O/L or higher.

At baseline, these groups had similar conventional lung function parameters, but the group with high reactance had significantly more abnormal impedance barriers, the researchers said.

Except for percent change in X₅, which was higher in the group with high reactance, the percent changes in the oscillatory parameters in response to methacholine were similar in both groups as well.

The high reactance group had greater absolute magnitudes of R₅, R_5-19 and X₅ at peak methacholine as well as lower tidal volume. The low reactance group had stronger and more significant correlations between changes in impedance parameters and percent change in FEV₁, the researchers continued, especially R_5-19, indicating greater concordance between central and peripheral airway behavior during bronchoconstriction.

When the researchers compared the patients in the high reactance group who were and who were not using inhaled corticosteroids, they said they did not find any differences in oscillometry responses or airway reactivity level.

The researchers also speculated that greater peripheral dysfunction and not greater central airway dysfunction may be causing the discordance between the changes in impedance parameters and change in FEV₁ among the patients in the high reactance group.

Similar changes in resistance at 19 Hz and greater changes in R₅ and X₅ as measured by oscillometry support this possibility, the researchers continued, also noting that the high reactance group had this peripheral dysfunction at baseline as well.

Further, the high reactance group was all women. The group additionally had a higher prevalence of gastroesophageal reflux disease and greater likelihoods of using inhaled corticosteroids and requiring systemic corticosteroids in the previous 12 months for an asthma exacerbation.

These patients also had numerically lower IgE, clinically but not statistically significant higher Asthma Control Scores and more frequent wheeze and chest tightness in the previous month.

Overall, the researchers said the changes in impedance parameters in response to methacholine did not distinguish the control patients from those with asthma in a population of patients with obesity.

But since those patients with asthma responded at slightly lower concentrations of methacholine, the researchers continued, obesity may predispose patients to reactivity in peripheral airways regardless of whether they have asthma.

Finally, the researchers concluded, these results further suggest two distinct physiological phenotypes of asthma with obesity, with one appearing in an early onset allergic form and the other in a late-onset nonallergic form.

“These [findings] are important as the majority of people with severe asthma have obesity, and so we may need to rethink how we assess disease in these people,” Dixon said.

“If people with obesity and asthma have relatively normal lung function as measured by spirometry, but a lot of symptoms, they likely need further testing to assess whether they have small airway dysfunction,” she continued. “In our study, we did this by oscillometry.”

Next, the researchers aim to determine if treatments that target small airway closure could help these patients.

“We are currently studying whether CPAP might be helpful in this patient population,” Dixon said.

For more information:

Anne E. Dixon, MA, BM, BCh, can be reached at anne.dixon@uvmhealth.org.