Corticosteroid, bronchodilator therapy may improve symptoms in children with long COVID

Daily inhaled corticosteroid and bronchodilator therapy may help children with reversible peripheral airway obstruction and lung hyperinflation after developing persistent dyspnea despite normal spirometry, according to a recent case study.

This dyspnea often develops after SARS-CoV-2 infection, Nathan Rabinovitch, MD, MPH, pediatric allergist and immunologist at National Jewish Health, and colleagues wrote in the study, published in The Journal of Allergy and Clinical Immunology: In Practice.

The case study

In the case study, the researchers described a Hispanic boy aged 17 years who developed COVID-19 in November 2020. Symptoms included severe shortness of breath and decreased exercise tolerance that persisted for the next 5 months.

Prescribed treatment began with fluticasone metered-dose inhaler (MDI) 110 and albuterol MDI and then changed to fluticasone/salmeterol 115 MDI. However, the patient’s adherence was poor, and he took his inhalers without using a spacer.

But the patient still reported some improvements in exercise tolerance when he did take his medication, and the researchers reported that he was able to walk on a treadmill for 5 minutes before shortness of breath began.

The patient had no prior diagnosis of asthma, wheezing episodes or recurrent bronchitis. Also, skin prick testing for 23 aeroallergens was negative. Evaluation by a behavioral specialist did not reveal any significant anxiety or depression.

Other presentations included normal FEV₁ percent predicted (97%) and FEV₁ to forced vital capacity ratio (0.81).

According to the researchers, 7.5 minutes of bike exercise testing reproduced the patient’s dyspnea symptoms via real-time laryngoscopy without any significant decrease in FEV₁, hyperventilation or vocal cord adduction.

The patient also experienced moderately increased hyperinflation (149%,) with a normal ratio of residual volume (RV) to total lung capacity (TLC) of 24 via plethysmography.

Additionally, the patient had increased percent peripheral airway resistance (44% of total airway resistance) based on measurement of resistance at 5 Hz – 20 Hz (R5-R20).

The researchers considered his 56% decrease from baseline in small airway reactance as measured by the area under the curve from R5 to resonant frequency (AX) to be significantly reversible as well.

The patient was then prescribed two puffs of fluticasone 44 each day and two puffs of albuterol before exercise in addition to using the proper spacer technique, along with slowly increasing his exercise regimen.

Three months later, the patient was able to exercise vigorously with marked improvements in shortness of breath. Although his AX response to albuterol continued to be significantly elevated, with a 51% decrease from baseline, his R5-R20/R5 decreased to 12.5% of total lung resistance.

The researchers then concluded that this patient’s predominantly small airway obstruction and airway hyperinflation contributed to his dyspnea and exercise intolerance.

Other patients, recommendations

This patient was one of 50 children with post-COVID dyspnea evaluated by the researchers, with most demonstrating increased RV and/or RV/TLC, high R5-R20/R5 or AX reversibility with albuterol.

The researchers also noted that FEV₁ reactivity to methacholine was sometimes present among these children, although most of them did not demonstrate low FEV₁ percent predicted or significant FEV₁ reversibility after albuterol.

Most of these patients did not have a previous diagnosis of asthma or treatment with asthma medications. Those who did had nonpersistent asthma before COVID-19, and only one had taken daily corticosteroids.

Overall, these children experienced improved small airway resistance with albuterol and/or lung hyperinflation, with almost all of them reporting at least partial improvements in dyspnea and improvements in exercise intolerance with inhaled corticosteroid therapy, with or without long-acting beta 2 agonists.

Although R5-R20 levels decreased among these patients as well, the researchers continued, they did not normalize in all cases, indicating potential long-term changes in the airway.

Symptoms continued to decrease for these children as they maintained their medication and exercise regimens, but some of these improvements likely were due to the natural course of the disease as well, the researchers wrote.

Based on these findings, the researchers recommended that the potential contribution of small airway reversible obstruction and lung hyperinflation should be assessed in children with post-COVID dyspnea and exercise intolerance, along with anxiety, dysautonomia and vocal cord dysfunction.

Physicians also should initiate sustained trials of asthma controller medications and slowly increase exercise intensity among patients who meet these criteria as their spirometry often is normal, the researchers concluded.