Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial

To study the efficacy of intermittent tiotropium bromide treatment in conjunction with albuterol sulfate in early childhood (<3 years old) episodic wheezing in comparison with regimens containing albuterol sulfate with or without fluticasone propionate.

Eighty patients were recruited across 4 hospitals in Finland aged 6 to 35 months, and with 2 to 4 physician confirmed episodes of wheeze and/or shortness of breath. Exclusion criteria included other primary pulmonary diagnoses, regular use of asthma controller medication, or other chronic diseases.

Subjects were randomized to 3 treatment arms to use as needed over a 48-week period. The arms included intermittent tiotropium bromide 5 ug administered with as-needed albuterol sulfate 0.2 mg 4 to 6 times daily (tiotropium group), intermittent fluticasone propionate 125 ug initiated twice daily at the onset of respiratory viral symptoms for 7 to 14 days along with as-needed albuterol 4 to 6 times daily (fluticasone group), or as-needed albuterol sulfate 0.2 mg treatment 4 to 6 times daily (albuterol group). Outcomes included diaries of respiratory symptoms and additional medication use. Background information included demographic and environmental data, as well as sensitization to food and aeroallergens and peripheral blood eosinophilia.

The tiotropium group had significantly more episode-free days (median 97%) compared with the fluticasone group (median 87%) or the albuterol group (median 88%) in spite of allergic sensitization, number of physician-confirmed episodes of wheeze, and/or shortness of breath before enrollment, or short-course glucocorticoid treatment in the 2 weeks before enrollment. The tiotropium group had less troublesome respiratory symptoms than the albuterol group, and less albuterol usage than either group.

Intermittent tiotropium may be an effective add-on treatment of episodic wheezing in toddlers. Tiotropium is suggested as an alternative, nonsteroidal treatment of earlier treatment of wheezing.

Tiotropium bromide is an effective treatment in older individuals with asthma, and this study is the first assessing the efficacy of tiotropium in younger children. It appears to be an effective and well tolerated medication, and fits with existing knowledge surrounding variable response to albuterol for lower respiratory tract wheezing episodes. Future directions include further phenotyping and endotyping to better understand which patient profiles may benefit from use.