In patients who died of asthma, inflammation extends beyond the airway smooth muscle and is still significant around the pulmonary arterioles. Kraft and colleagues13 have shown alveolar inflammation in patients with nocturnal asthma (NA), which is not the case in those with non-NA (NNA). Patients with NA had increased numbers of eosinophils per lung volume in their lung parenchyma at 4:00 am compared to patients without NA, and the NA patients had a greater number of eosinophils and macrophages in their alveolar tissue at 4:00 am than at 4:00 pm. In addition, in NA patients, only alveolar (and not central airway) eosinophilia correlated with an overnight reduction in lung function.,13Those same investigators14 have shown increased numbers of CD4+ cells in the alveolar tissue of NA patients at 4:00 am compared to those found in NNA patients. Although the number of CD4+ cells in the endobronchial lamina propria was higher than that in the alveolar tissue, once again, only the alveolar tissue CD4+ lymphocytes correlated with the predicted lung function (ie, FEV1) at 4:00 am (r = −0.68) and with the number of activated alveolar eosinophils (r = 0.66).,14 In this same patient cohort, NA was associated with reduced glucocorticoid receptor (GR)-binding affinity, reduced proliferation of blood mononuclear cells, and decreased responsiveness to steroids at 4:00 am compared to those in NNA patients.,17 Those studies have proposed that the increased numbers of CD4+ cells in the alveolar tissue of NA patients, the reduced GR-binding affinity, and the reduced steroid responsiveness may be responsible for orchestrating eosinophil influx and exacerbations of symptoms in patients with NA. One of the mechanisms that may be responsible for this phenomenon is an up-regulation of GRβ, which has been reported previously12 in the peripheral airways of steroid-insensitive subjects with severe asthma. The main cells expressing GRβ were CD3+ T lymphocytes and, to a lesser extent, eosinophils, neutrophils, and macrophages.12 Those results suggested that the increased number of GRβ-positive cells in the distal airways of patients with fatal asthma may be associated with steroid resistance, contributing to asthma mortality.