A new development which has emerged from this Department marks the beginning of an expansion into other foods besides cereals. It also marks the beginning of the wider use of fluorescence in monitoring and controlling food processing.
Recently there have been important advances in our understanding of muscarinic receptors in airways that have important implications for understanding airway control and for future therapy of airway diseases. The transduction mechanisms involved in muscarinic receptor activation are now better understood. Receptor-linked phosphoinositide hydrolysis leads to release of calcium ions from intracellular stores, resulting in contraction of airway smooth muscle. At least five subtypes of muscarinic receptor have now been cloned, although only three subtypes can be distinguished pharmacologically. M1 receptors are facilitatory to neurotransmission in airway parasympathetic ganglion cells and have also been identified in airway submucosal glands and on the alveolar walls of human lung. M2 receptors are located on postganglionic nerves and function as powerful feedback inhibitory receptors (autoreceptors) that are likely to be involved in modulation of reflex bronchoconstriction. These receptors may be dysfunctional in asthmatic airways. M3 receptors are present on airway smooth muscle and submucosal glands and mediate the classical muscarinic effects in airways. Molecular biology techniques should now allow further study of the factors that regulate transcription and expression of muscarinic receptors in airways.
Alveolar macrophages play a critical role in the pathophysiology of COPD and are a major target for future anti‐inflammatory therapy. Macrophage numbers are markedly increased in the lung and alveolar space of patients with COPD and are localized to sites of alveolar destruction. The increased numbers of macrophages may result from increased recruitment of blood monocytes, prolonged survival in the lung and to a lesser extent to increased proliferation in the lung. Alveolar macrophages from COPD patients have an increased baseline and stimulated secretion of inflammatory proteins, including certain cytokines, chemokines, reactive oxygen species and elastolytic enzymes, which together could account for all of the pathophysiological features of COPD. Alveolar macrophages form COPD appear to be resistant to the anti‐inflammatory effects of corticosteriods and this is linked to reduced activity and expression of histone deacetylase 2, a nuclear enzyme that switches off inflammatory genes activated through the transcription factor nuclear factor‐KB. Alternative anti‐inflammatory therapies that inhibit macrophages are therefore needed in the future to deal with the chronic inflammation of COPD. These drugs may include resveratrol, theophylline derivatives, MAP kinase inhibitors and phosphodiesterase‐4 inhibitors.
In asthma there is increased vascularity of the airway mucosa, altering heat loss in the airways. We hypothesized that as a result of these inflammatory changes, asthmatic patients would have elevated rates of the exhaled air temperature increase (Deltae degrees T). We measured Deltae degrees T in 18 asthmatic subjects (mean age +/- SEM, 38 +/- 8 yr; 9 male, FEV(1) 74 +/- 10%) and 16 normal volunteers (mean age +/- SEM, 33 +/- 3 yr) and compared it with exhaled nitric oxide (NO) as a marker of inflammation. Deltae degrees T was measured during a flow- and pressure-controlled single exhalation with a fast response (1 ms) thermometer. The end-expiratory plateau temperature was similar in asthmatic compared with normal subjects (35.75 +/- 0.6 degrees C and 34.45 +/- 0.8 degrees C, p > 0.05). However, Deltae degrees T was greater in asthmatic subjects (8.17 +/- 0.83 degrees C/s and 4.12 +/- 0.41 degrees C/s, p < 0.01) and correlated with NO (r = 0.65, p = 0.034). Deltae degrees T was increased in normal subjects (from 4.28 +/- 0.8 degrees C/s to 7.60 +/- 0.5 degrees C/s, p < 0.01) but not in asthmatic patients (from 8.28 +/- 0.41 degrees C/s to 8.80 +/- 0.41 degrees C/s, p > 0.05) after the inhalation of albuterol, indicating that Deltae degrees T may reflect bronchial blood flow. Asthmatic subjects have elevated Deltae degrees T. This may represent a novel, noninvasive means of measuring airway blood flow and inflammation in asthma.