Lessons learned from clinical trials of asthma

Paul A. Greenberger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Exacerbations of persistent or intermittent asthma should be anticipated by physicians and health-care professionals. Patients who are likely to experience an exacerbation often have a history of an exacerbation in the previous year, and the absolute eosinophil count in peripheral blood is ≥ 400/μL. Similarly, expectorated or induced sputum eosinophilia of ≥2% is associated with exacerbations. These phenotypic findings have led to effective biologic therapies, which target eosinophils or immunoglobulin E or the T-helper type 2 phenotype, especially in children, adolescents, and adults with frequent exacerbations. In children, a reduced forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity ratio can be associated with future exacerbations, although the FEV1 may be in the normal range, even with children who have persistent severe asthma. Asthma control questionnaires did not differentiate between children with or children without a future exacerbation. Alternatively, in adults, the lower baseline FEV1 (2.3 L [74% predicted] versus 2.5 L [78% predicted]) identified patients more likely to have a future exacerbation compared with patients who were not having an exacerbation. After correcting for FEV1, the asthma control questionnaire data were associated with exacerbations. In adolescents (ages ≥ 12 years) and adults with persistent mild asthma, most (73%) did not have sputum eosinophilia, and some of these patients responded well to the anticholinergic, tiotropium, which would argue differently from administration of an inhaled corticosteroid as first-line controller therapy. In a three-track study of patients with persistent mild asthma, as-needed budesonide-formoterol and scheduled budesonide were associated with approximately one-half of the annual exacerbation rate of as-needed albuterol. In patients with persistent moderate-to-severe asthma, tiotropium added to controller therapy caused an increase in FEV1 without improving the asthma control questionnaire findings. There were two studies that explored whether either quadrupling or quintupling the inhaled corticosteroid at the first sign of loss of control of asthma would provide meaningful reductions of severe exacerbations of asthma, but the findings did not support this strategy. Both biologic therapies and environmental control (dust mite impermeable encasings) have resulted in reductions of exacerbations in patients with persistent moderate and severe asthma.

Original languageEnglish (US)
Pages (from-to)410-413
Number of pages4
JournalAllergy and asthma proceedings
Volume40
Issue number6
DOIs
StatePublished - Nov 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pulmonary and Respiratory Medicine

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