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PubMed2004

Role of nasal nitric oxide in the resolution of experimental rhinovirus infection.

BACKGROUND: Human rhinovirus (HRV) infections are associated with exacerbations of asthma, chronic obstructive pulmonary disease, and sinusitis. Nitric oxide (NO) might play an important role in host defense through its potent antiviral properties. Previous studies have shown that HRV infection in human subjects increased nasal epithelial expression of type 2 nitric oxide synthase (NOS2), an isoform of the enzyme that produces NO. OBJECTIVE: We sought to investigate whether increases in exhaled NO (eNO) would accompany the increased NOS2 expression and would be associated with clearance of the virus. METHODS: Six human subjects were infected with HRV-16 intranasally. eNO from nasal and lower airways was measured by means of direct measurement at multiple controlled flow rates. eNO was monitored at baseline (day 1) and on days 2 to 5, 8, 14, and 42 after infection. Nasal lavages were performed on days 1 to 5 and 8, and nasal scrapings were performed on days 1 to 4. NOS2 mRNA expression in nasal cells was measured by using quantitative real-time RT-PCR. Viral shedding in nasal lavage fluid was monitored by using real-time RT-PCR and bioassay. RESULTS: Peak HRV titers and symptom scores were correlated on day 3, and HRV persisted until day 5 (n=4) or day 8 (n=2). Infection was associated with transient but significant increases in lymphocytes and monocytes in nasal lavage fluid. Significant increases in both nasal and lower airway eNO concentrations accompanied HRV infection and were positively correlated. Increased nasal eNO concentrations on day 3 were associated with increased expression of NOS2 mRNA in nasal scrapings. Symptom scores on day 4 were inversely correlated with the increases in nasal eNO concentration. CONCLUSIONS: We conclude that increased production of NO occurs as part of the host response to HRV infection and speculate that NO plays a beneficial role in viral clearance.

Common Cold↗

PubMed1984

The clinical application of fibroblast interferon--an overview.

Preclinical as well as clinical studies with fibroblast interferon (IFN) are still lagging behind on those with leukocyte interferon. Its side-effects seem to be less pronounced than those of human IFN-alpha, yet it may be slightly pyrogenic after intravenous injection. Pyrogenicity of current impure preparations might for the larger part be due to impurities. Higher doses of HuIFN-beta than of HuIFN-alpha are required to obtain measurable blood titers by intramuscular injections. Since there is concern about this being due to destruction of the interferon before it has reached its target organ(s), most current clinical studies use either local (e.g. intratumoral) treatment or intravenous infusions. A study of topical treatment for acute rhinovirus infection has indicated that there is very little if any chance for fibroblast interferon to be a clinically useful substance to prevent or cure common cold. In herpetic dendritic keratitis eye drops of fibroblast interferon may be useful as such or in combination with debridement. Topical treatment of warts (multiple intralesional injections) has been shown to yield a high success rate, especially in the case of verrucae vulgares, but less so in the case of verrucae planae juveniles. Studies on condyloma accuminatum are not so far advanced as to permit a documented conclusion. Topical (intralesional) treatment of neoplastic diseases has been investigated, especially in Japan, to demonstrate that fibroblast interferon does have an antineoplastic effect in vivo. While there seems to be little doubt that local delivery does indeed cause tumor nodules to regress, the question is whether this procedure can offer a true clinical benefit to the patient. Systemic (intravenous) administration for chronic hepatitis B has been investigated further: given alone or in combination with adenine-arabinoside, fibroblast interferon seems to be able to reduce the level of viral activity. Whether this will lead to a generally accepted treatment of chronic active hepatitis is difficult to say at this moment. In treating herpes zoster in cancer patients, results have been obtained which are comparable to those found for leukocyte interferon. The practical significance of this finding must be seen in the perspective of recent developments in the chemotherapy of herpes zoster. In breast cancer patients given intramuscular injections, metastases in the skin, but not in other organs, showed alterations suggestive of an effect on tumor progression. Yet there was no true clinical benefit for the patient. In other tumors, e.g. head and neck epithelioma, no effect was seen.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Topical↗

PubMed1996

A cloud adult: the Staphylococcus aureus-virus interaction revisited.

BACKGROUND: Nasal carriage of Staphylococcus aureus is common among health care workers, but outbreaks caused by such carriers are relatively uncommon. We previously reported outbreaks of S. aureus skin infections that affected newborn infants and were attributed to an S. aureus nasal carrier who had had an associated upper respiratory tract infection (UR) during the outbreak period. OBJECTIVE: To investigate the contribution of a nasal methicillin-resistant S. aureus (MRSA) carrier (physician 4) who contracted a URI to an outbreak of MRSA infections that involved 8 of 43 patients in a surgical intensive care unit during a 3-week period. DESIGN: An epidemiologic study of an outbreak of MRSA infections and a quantitative investigation of airborne dispersal of S. aureus associated with an experimentally induced rhinoviral infection. SETTING: A university hospital. PARTICIPANTS: 43 patients in a surgical intensive care unit and 1 physician. MEASUREMENTS: Molecular typing was done, and risk factors for MRSA colonization were analyzed. Agar settle plates and volumeric air cultures were used to evaluate the airborne dispersal of S. aureus by physician 4 before and after a rhinoviral infection and with or without a surgical mask. RESULTS: A search for nasal carriers of MRSA identified a single physician (physician 4); molecular typing showed that the MRSA strain from physician 4 and those from the patients were identical. Multivariate logistic regression analysis identified exposure to physician 4 and duration of ventilation as independent risk factors for colonization with MRSA (P < or = 0.008). Air cultures showed that physician 4 dispersed little S. aureus in the absence of a URI. After experimental induction of a rhinovirus URI, physician 4's airborne dispersal of S. aureus without a surgical mask increased 40- fold; dispersal was significantly reduced when physician 4 wore a mask (P < or = 0.015). CONCLUSIONS: Physician 4 became a "cloud adult," analogous to the "cloud babies" described by Eichenwald and coworkers who shed S. aureus into the air in association with viral URIs. Airborne dispersal of S. aureus in association with a URI may be an important mechanism of transmission of S. aureus.

Adult↗