Asthma and Natural Colds

Abstract

We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus). In the subjects with confirmed virus infection, five of the asthmatics had an objective exacerbation of asthma during the cold. Their sputum on Day 4 showed a high median total cell count of 19.7 x 10(6) cells/ml with a modest neutrophilia (58. 5%) and high levels of interleukin-8 (IL-8) (16,000 pg/ml), eosinophilic cationic protein (ECP) (1,880 microgram/L) and very high levels of fibrinogen (250 mg/L). In contrast, the proportion (1.3%) and absolute number of eosinophils was low. IL-2 levels were within the normal range, whereas IL-5 and interferon gamma were under the limit of detection of the assays. In the healthy subjects with a confirmed virus infection the sputum findings were qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was strongly correlated with neutrophils (rs = 0.8, p < 0.001). This correlation was also significant when each group was analyzed separately. On Day 21 there was a fall in the absolute number of neutrophils and in ECP and fibrinogen levels in both groups. Similar results were found in the two asthmatic and three healthy subjects with a cold of comparable severity but in whom viral infection was not confirmed. We conclude that induced sputum examination can be used to study the effects of natural colds and influenza on the airways of the lungs. The results also suggest that natural colds, on Day 4, cause neutrophilic lower airway inflammation that is greater in asthmatics than in healthy subjects. The greater inflammatory response in asthmatics may be due to the changes associated with trivial eosinophilia or to the different viruses involved.

Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease

“…This is the first study to detect such a high incidence of rhinovirus infection during COPD exacerbations and also the first to show that wild-type rhinovirus is very likely to infect the lower airway in COPD patients. Positive PCR reactions were confirmed by DNA sequencing, although previous studies of natural rhinovirus infection have not used sequencing [6,17,18].…”

Phosphatidylinositol 3-Kinase Is Required for Rhinovirus-induced Airway Epithelial Cell Interleukin-8 Expression

“…RV is also an important trigger of COPD exacerbations (3,4). Clinical studies suggest that RV may stimulate exacerbations of asthma and COPD by inducing bronchial epithelial cell production of IL-8, leading to a neutrophilic inflammatory response (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Little is known about the biochemical signaling pathways regulating RV-induced IL-8 expression, however.…”

“…IL-8 and neutrophils are found in the nasal secretions and sputum of patients with RV-induced asthma exacerbations (5)(6)(7)(8)(9). Further, the number of neutrophils correlates with the level of IL-8 (7,9). RV induces IL-8 expression in cultured airway epithelial cells (10 -12).…”

Corticosteroids and β2 Agonists Differentially Regulate Rhinovirus-induced Interleukin-6 via Distinct Cis-acting Elements

“…Recent evidence suggests a large proportion of exacerbations of both diseases are precipitated due to viral infections (1)(2)(3)(4)(5)(6)(7), and the most prominent respiratory virus associated with either disease is human rhinovirus (RV) (8 -10). Rhinovirus infects the bronchial epithelium and induces a variety of proinflammatory cytokines, chemokines, and adhesion molecules, serving to attract inflammatory cells and prolong local inflammation within the airway (11,12). Among the many cytokines induced, IL-6, a pleiotropic cytokine, is commonly associated with both diseases (13)(14)(15).…”