Ronald B. Turner

Epidemiology, Pathogenesis, and Treatment of the Common Cold

Objective Reading this article will reinforce the readers knowledge of the pathogenesis of the common cold. The rationale for current and potential therapies for the common cold are reviewed in the context of current concepts of the pathogenesis of these illnesses. Data sources and study selection A MEDLINE literature search was done using the search terms common cold, rhinovirus, and viral respiratory infection. The search was restricted to the English language. Articles were selected for review if the title and/or abstract suggested the content was relevant to the subject of this review. The bibliographies of selected articles were used as a source of additional literature. Results Recent studies suggest that the host response to the virus is an important contributor to the pathogenesis of the common cold. Inflammatory mediators, especially the pro-inflammatory cytokines, appear to be an important component of this response and present an attractive target for new interventions for common cold therapies. Currently available treatments for the common cold have limited efficacy against specific symptoms. These therapies should be selected to treat the specific symptoms that are perceived to be the most bothersome by the patient.

The treatment of rhinovirus infections: progress and potential.

The common cold is an important illness both as a result of the economic impact of this common disease and because of the morbidity associated with the complications of the illness. Recent attempts to develop antiviral treatments for the common cold represent a substantial advance over previous efforts. Formidable barriers remain to be overcome, however, before any of these new products will be proven to be clinically useful. Recent advances in our understanding of the pathogenesis of common cold symptoms have provided insights into potential new targets for the treatment of this illness.

Effect of Treatment with Zinc Gluconate or Zinc Acetate on Experimental and Natural Colds

Two clinical trials were conducted, one involving 273 subjects with experimental rhinovirus colds and the other involving 281 subjects with natural colds. Symptomatic volunteers were randomized to receive oral lozenges containing zinc gluconate (13.3 mg), zinc acetate (5 or 11.5 mg), or placebo. The median duration of illness in zinc gluconate recipients was 2.5 days, contrasted with 3.5 days in the placebo recipients (P=.035), in the experimental colds study. Zinc gluconate had no effect on symptom severity and zinc acetate had no effect on either duration or severity. Neither formulation had an effect on the duration or severity of natural cold symptoms. Evaluation of blinding, taste, and adverse events revealed no significant differences among the 4 treatment arms. Zinc compounds appear to have little utility for common-cold treatment.

The role of oxidative stress in rhinovirus induced elaboration of IL-8 by respiratory epithelial cells

A direct correlation has been reported between the severity of symptoms associated with rhinovirus infection and the concentration of interleukin-8 in nasal secretions. The purpose of these studies was to examine the mechanism of rhinovirus-induced IL-8 elaboration. Rhinovirus infection induced oxidative stress in Beas-2b cells and the concentration of H2O2 in supernatant media from rhinovirus challenged cells was 12.5 +/- 6.1 microM 1 h after challenge compared to 0.7 +/- 0.3 microM in supernatant from control cells. N-acetyl cysteine inhibited RV-induced NF-kappaB activation and IL-8 elaboration. IL-8 concentrations were 36 +/- 2 pg/ml and 10 +/- 1 pg/ml 6 h after virus challenge in untreated and NAC-treated (30 mM NAC) cells, respectively. Despite the effects of NAC on IL-8 elaboration and NF-kappaB activation, RV stimulated increases in supernatant H2O2 were not altered by NAC. These data suggest that RV stimulation of IL-8 in respiratory epithelium is mediated through production of oxidative species and the subsequent activation of NF-kappaB.

Accuracy of Radiographic Differentiation of Bacterial from Nonbacterial Pneumonia

The chest roentgenogram is an accepted tool for the diagnosis of pneumonia. Little information is available, however, addressing the ability of physicians to distinguish bacterial from nonbacterial pneumonias by examination of the chest roentgenogram. Five different observers evaluated 36 chest films from patients with pneumonia who had a laboratory proven etiologic diagnosis. The sensitivity of roentgenogram diagnosis of bacterial pneumonia ranged from 42-58 percent. When clinical and laboratory data were provided to the observers the sensitivity ranged from 42-92 percent. This study indicates that chest film examination is too insensitive to be useful for the selection of patients who have bacterial pneumonia from those whose pneumonia is non-bacterial.

Rhinovirus-Induced Oxidative Stress and Interleukin-8 Elaboration Involves p47-phox but Is Independent of Attachment to Intercellular Adhesion Molecule-1 and Viral Replication

Abstract Virus-induced elaboration of proinflammatory cytokines is mediated by virus-induced oxidative stress. The purpose of these studies was to determine the source of the virus-induced oxidative stress. Inhibition of viral replication with antibody to intercellular adhesion molecule-1 had no effect on virus-induced oxidative stress or interleukin-8 (IL-8) response (597 ± 88 vs. 668 ± 78 pg/mL in control cells). Treatment of cells with diphenylene iodonium inhibited virus-induced oxidative stress and IL-8 elaboration, but allopurinol, ibuprofen, and rotenone had no effect. Studies in cell lines produced from a patient with gp91-phox deficiency revealed normal responses. In contrast, the oxidative response was decreased and the IL-8 concentration was 227 ± 36 pg/mL in cells from a patient with p47-phox deficiency, compared with 664 ± 48 pg/mL in control cells. These studies suggest that the stimulation of reactive oxygen species by viral challenge occurs at the cell surface even in the absence of viral replication and involves a flavoprotein that may act in concert with p47-phox.

Effects of an experimentally induced rhinovirus cold on sleep, performance, and daytime alertness

Abstract Study objectives: There is accumulating evidence that the common cold produces impairments in psychomotor vigilance. This has led some investigators to hypothesize that such illnesses may also have disruptive effects on sleep. While several self-report studies suggest that viral illness may influence sleep parameters, no studies have assessed polysomnographically recorded sleep following viral infections. Design: Parallel control group comparison. Setting: Sleep laboratory in a large urban medical center. Participants: Twenty-one men and women with susceptibility to the rhinovirus type 23. Interventions: Nasal inoculation with rhinovirus type 23. Measurements: Polysomnographically recorded sleep for five nights (2300–0700 h) post-viral inoculation. Twice daily (1030 and 1430 h) performance assessment during each experimental day using auditory vigilance and divided attention tasks. A multiple sleep latency test (MSLT) was performed daily for the duration of the study. Results: In symptomatic individuals, total sleep time decreased an average of 23 min, consolidated sleep decreased an average of 36 min, and sleep efficiency was reduced by an average of 5% during the active viral period (experimental days/nights 3–5) compared with the incubation period. Psychomotor performance was impaired. These changes were significantly greater than those observed in asymptomatic individuals. Conclusions: The common cold can have detrimental effects on sleep and psychomotor performance in symptomatic individuals during the initial active phase of the illness.

Assessment of adherence with medications in human immunodeficiency virus-infected children.

The purpose of this study was to determine the reliability of screening for medication adherence in HIV-infected children. The results suggest that caregivers who are unable to describe the medication regimen or who are nonadherent with appointments are unlikely to adhere to the medication regimen. Adherence with at least 90% of medication doses was associated with a virologic response.

Interleukin-1 and Nitric Oxide Increase NADPH Oxidase Activity in Human Coronary Artery Smooth Muscle Cells

Objective: Cytokines, nitric oxide (NO) and reactive oxygen species (ROS) are well known for their pathogenic effects in development of cardiovascular diseases. Interleukin-1β (IL-1β) is known to induce NO generation, however it is not well established if IL-1β or NO regulate production of ROS, such as superoxide anion. Therefore, the main objective of this study was to evaluate the effect of IL-1β or NO on enzyme activity of NADPH oxidase (NOX), a superoxide-generating system recently documented to participate in a variety of vascular functions. Methods: Human coronary artery smooth muscle cells (SMC) obtained from Clonetics were treated with IL-1β and NO donor, sodium nitroprusside (SNP), in culture. Nitrites accumulated in supernatants of SMC cultures were measured as an index of NO released following treatment with IL-1β. NOX enzyme activity was assayed using cytochrome c as the electron acceptor. Results: Treatment with IL-1β resulted in a 3-fold increase in the production of NO by SMC. Both IL-1β and SNP enhanced NOX activity, by 67 and 45%, respectively, following 24 h of treatment. Conclusion: This study suggests that NO or NO- generating cytokines might regulate the production of ROS in the cardiovascular system through modulation of superoxide-generating systems such as NOX.

The epidemiology, pathogenesis, and treatment of the common cold

Objective: Reading this article will reinforce the reader’s knowledge of the pathogenesis of the common cold. The rationale for current and potential therapies for the common cold are reviewed in the context of current concepts of the pathogenesis of these illnesses. Data Sources and Study Selection: A MEDLINE literature search was done using the search terms common cold, rhinovirus, and viral respiratory infection. The search was restricted to the English language. Articles were selected for review if the title and/or abstract suggested the content was relevant to the subject of this review. The bibliographies of selected articles were used as a source of additional literature. Results: Recent studies suggest that the host response to the virus is an important contributor to the pathogenesis of the common cold. Inflammatory mediators, especially the pro-inflammatory cytokines, appear to be an important component of this response and present an attractive target for new interventions for common cold therapies. Currently available treatments for the common cold have limited efficacy against specific symptoms. These therapies should be selected to treat the specific symptoms that are perceived to be the most bothersome by the patient. Ann Allergy Asthma Immunol 1997;78:531–40.