Asthma Exacerbations in Urban Children

We performed a retrospective analysis of data from a prospective observational cohort study (MUPPITS1)^{17 (link)} and validated our findings with data from a randomised, double-blind, placebo-controlled trial in an independent cohort (ICATA).^{18 (link)}The MUPPITS1 study was a longitudinal observational study of 208 children with exacerbation-prone asthma in low-income urban centres, who were followed up between 2015 and 2017 for respiratory illnesses. This study has previously been described elsewhere.^{17 (link)} Briefly, participants were recruited between Oct 7, 2015, and Oct 18, 2016, across hospital clinics in major urban areas in nine US cities. An individual was eligible for enrolment if they were aged 6–17 years; were diagnosed with asthma by a clinician more than 1 year before recruitment; had at least two asthma exacerbations (ie, required systemic corti costeroids or hospital admission, or both) in the year before recruitment; were treated with at least one puff of fluticasone 250 μg twice daily, or its equivalent for children aged 6–11 years, or treated with at least one puff of fluticasone 250 μg plus salmeterol 50 μg twice daily, or its equivalent for children aged 12 years and older; had more than or equal to 150 peripheral blood eosinophils per mm³; did not smoke; and lived in a census tract with a density of more than or equal to 1000 families per square mile and with at least 10% of families with income below the poverty level (based on American Community Survey data¹⁹ ). Participants were identified for recruitment through the Registry for Asthma Characterization and Recruitment 2 and site-approved recruitment sources (NCT02513264). Participants were followed up prospectively for up to two respiratory illnesses or approximately 6 months, whichever occurred first. Participants who reported a respiratory illness were asked to return to the clinic twice in the 6-day period after the start of symptoms for collection of nasal samples and pulmonary function testing. Each illness was defined as a viral (V+) or non-viral (V–) event on the basis of virological assessment of the first nasal blow sample by use of the Luminex Respiratory Viral Panel (Luminex, Austin, TX, USA), with (Ex+) or without an asthma exacerbation (Ex–) on the basis of whether the participant was treated with systemic corticosteroids within 10 days following the onset of the respiratory event or not (appendix p 11). The last study visit occurred on Jan 6, 2017.
The ICATA study was a randomised, double-blind, placebo-controlled trial of omalizumab conducted from 2006 to 2009 in 419 inner-city children, adolescents, and young adults (ie, aged 6–20 years) with persistent allergic asthma, as previously described.^{18 (link)} Briefly, participants were enrolled between Oct 23, 2006, and March 25, 2008, across hospital clinics in major urban areas in eight US cities. An individual was eligible for enrolment if they were aged 6–20 years; were diagnosed with asthma by a clinician more than a year before recruitment or diagnosed with asthma and had symptoms for longer than 1 year; had bodyweight and total serum IgE suitable for omalizumab dosing and a positive skin-prick test to at least one perennial allergen; did not smoke; and lived in a census tract with a density of more than or equal to 1000 families per square mile with and at least 10% of families with income below the poverty level. In an exploratory substudy of 189 of 419 participants in four of eight US cities (ie, New York, NY, Chicago, IL, Dallas, TX, and Cleveland, OH), 100 nasal samples were collected within 7 days of the onset of an asthma exacerbation (ie, required systemic corticosteroids; Ex+) and 165 nasal samples were collected at study week 48 in the absence of an exacerbation. The last study visit occurred on Dec 30, 2009. The nasal samples were used for virological assessment by use of the Eragen Multi-Code Respiratory Virus Panel (Eragen Biosciences, Madison, WI, USA) and defined as V+ or V–(appendix pp 12–13).
In this analysis, we included participants from the MUPPITS1 cohort who reported a respiratory event at some point during the follow-up and participants from the ICATA cohort who had nasal samples collected due to a respiratory event or at a scheduled visit. Sex was self-reported by participants, with the options of male or female.
The MUPPITS1 and ICATA protocols were approved by the Inner-City Asthma Consortium steering committee, protocol review committee, and data safety monitoring board. The MUPPITS1 protocol²⁰ was reviewed by a single institutional review board, and the ICATA protocol²¹ was reviewed by the institutional review boards of all participating institutions. Written informed consent for the MUPPITS1 and ICATA studies was obtained from the parents or legal guardians of all participants and applies to this analysis.