Increased expression of platelet-derived growth factor receptor-beta in airway fibroblasts of severe asthmatics.
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Asthma↗
Biomedical subjects
E Rand Sutherland
Publications and source records attributed to E Rand Sutherland.
Immunomodulatory effects of melatonin in asthma.
Patients with nocturnal asthma demonstrate circadian variations in airway inflammation. We hypothesized that melatonin, a circadian rhythm regulator, modulates circadian inflammatory variations in asthma. The effect of melatonin stimulation on peripheral blood mononuclear cell cytokine production was evaluated at 4:00 P.M. and 4:00 A.M. in normal control subjects, patients with nocturnal asthma, and patients with non-nocturnal asthma. Melatonin was proinflammatory, causing significantly increased production of interleukin-1, interleukin-6, and tumor necrosis factor-alpha at 4:00 P.M. and 4:00 A.M. in all subject groups (range, 12.8 +/- 3.3 to 131.72 +/- 16.4%, p < or = 0.0003). The observed increases in cytokine production did not change between 4:00 P.M. and 4:00 A.M. in control subjects or in patients with nocturnal asthma (p > 0.05, both cases). At 4:00 P.M., the cytokine response to melatonin of patients with nocturnal asthma was greater than that of control subjects or patients with non-nocturnal asthma and did not change significantly at 4:00 A.M. At 4:00 P.M., the cytokine response of patients with non-nocturnal asthma was less than that of patients with nocturnal asthma and rose significantly at 4:00 A.M. (p = 0.0001, all comparisons). Melatonin is proinflammatory in both patients with asthma and healthy subjects. Patients with nocturnal asthma demonstrate the largest daytime cytokine response and cannot be further stimulated at 4:00 A.M., suggesting chronic overstimulation in vivo. These results suggest differential immunomodulatory effects of melatonin based on asthma clinical phenotype and may indicate an adverse effect of exogenous melatonin in asthma.
Adjuvants, Immunologic↗
Distal lung inflammation in asthma.
OBJECTIVE: To review the role of distal lung inflammation in asthma. DATA SOURCES AND STUDY SELECTION: Selected peer-reviewed research publications retrieved from MEDLINE search. Search was restricted to English-language publications only. Included articles were selected for their relevance to pathophysiology, diagnosis, and treatment. Bibliographies of selected papers served as an additional source of considered publications. RESULTS: Inflammation in the small airways and alveolar tissue plays an important role in the clinical manifestations of asthma. Diagnostic modalities such as transbronchial biopsy and evolving radiologic techniques such as high-resolution computed tomography are improving our ability to evaluate this portion of the lung. New ultra-fine particle size metered-dose inhalers and oral agents such as cysteinyl leukotriene receptor antagonists offer new opportunities for treating small airways inflammation and need to be fully evaluated for their ability to target and treat distal lung inflammation. CONCLUSIONS: Distal lung inflammation is an important component of airway inflammation in asthma. New modalities for evaluating distal airway inflammation and for targeting the distal lung with inhaled and systemic drugs are rapidly expanding our knowledge of the clinical importance of distal lung inflammation and may ultimately be of critical importance in asthma therapy.
Administration, Inhalation↗
Safety of sputum induction in moderate-to-severe chronic obstructive pulmonary disease.
This retrospective study was designed to evaluate the safety and efficacy of a bronchoprotective sputum induction protocol in moderate to severe chronic obstructive pulmonary disease (COPD). Forty-two adults with COPD (FEV1 = 51.7 +/- 3.2% predicted (mean +/- SEM)) under went sputum induction using a protocol designed to minimize hypertonic saline-induced bronchoconstriction. Hypertonic (3%) saline was used for subjects with FEV1 > or = 50%, and normal (0.9%) saline was used for subjects with FEV1 < 50%. Primary outcomes were change in peak flow, FEV1 and oxygen saturation. Mean decline in peak flow during sputum induction was 13.2 +/- 2.1%. FEV1 fell by 11.4 +/- 2.3%, an absolute fall of 0.14 +/- 0.031. Oxygen saturation did not change. A fall in peak flow of > or = 20% reliably predicted a fall in FEV1 of > or = 20%. Thirty-five of 42 subjects (83.3%) produced an acceptable sputum sample. Sputum eosinophil and neutrophil percentages were 2.8 +/- 0.9 and 73.0 +/- 3.0%, respectively, and were not correlated with changes in peak flow, FEV1 or oxygen saturation. A protocol for sputum induction which restricts the use of hypertonic saline based on lung function is both safe and effective in subjects with moderate to severe COPD.
Adult↗