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Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

Aged↗

Rhinovirus infection of human embryonic lung fibroblasts induces the production of a chemoattractant for polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMNLs) appear in the nasal mucosa during rhinovirus colds before the onset of symptoms. This study describes a chemoattractant for PMNLs that is elaborated by human embryonic lung fibroblast cells infected with rhinovirus. Chemotaxis assays were done in a 48-well microchemotaxis chamber with normal adult PMNLs. Medium supernatants from rhinovirus-infected cell culture attracted 87 +/- 6 (mean +/- SE) PMNLs/10 high-power fields (x450) compared with 38 +/- 6 PMNLs/10 high-power fields attracted by medium from uninfected cell cultures (P less than .0001). Elaboration of the chemoattractant was not a result of cell destruction and did not require the presence of infectious virus. This chemoattractant produced by human fibroblast cells may contribute to the influx of PMNLs into the nasal mucosa during rhinovirus infection. The PMNLs may, in turn, have a role in producing symptoms of the common cold.

Cells, Cultured↗

Respiratory illness caused by picornavirus infection: a review of clinical outcomes.

BACKGROUND: Respiratory infections result from invasion of the respiratory tract, mainly by viruses, and are the leading cause of acute morbidity in individuals of all ages worldwide. During peak season, picornaviruses cause 82% of all episodes of acute nasopharyngitis (the common cold), the most frequent manifestation of acute respiratory infection, and produce more restriction of activity and physician consultations annually than any other viral or bacterial source of respiratory illness. OBJECTIVE: This article reviews the clinical impact and outcomes of picornavirus-induced respiratory infections in specific populations at risk for complications. It also discusses the potential economic impact of the morbidity associated with picornavirus-induced respiratory infection. METHODS: Relevant literature was identified through searches of MEDLINE, OVID, International Pharmaceutical Abstracts, and Lexis-Nexis. The search terms used were picornavirus, rhinovirus, enterovirus, viral respiratory infection, upper respiratory infection, disease burden, economic, cost, complications, asthma, COPD, immunocompromised, elderly otitis media, and sinusitis. Additional publications were identified from the reference lists of the retrieved articles. CONCLUSIONS: Based on the clinical literature, picornavirus infections are associated with severe morbidity as well as considerable economic and societal costs. Future research should focus on identifying patterns of illness and the costs associated with management of these infections. New treatments should be assessed not only in terms of their ability to produce the desired clinical outcome, but also in terms of their ability to reduce the burden of disease, decrease health care costs, and improve productivity.

Age Factors↗

Antiviral effect of 3, 4-dihydro-1-isoquinolineacetamide hydrochloride in experimental human rhinovirus infection.

Double-blind trials were conducted in volunteers to evaluate the efficacy of the prophylactic 3,4-dihydro-1-isoquinolineacetamide hydrochloride (DIQA) treatment against rhinovirus type 24 challenge. Ten men received a 7-day course of DIQA treatment and 11 men received a placebo. The intranasal viral challenge dose was 10 mean tissue culture infective doses. The oral administration of 1 g prechallenge and 2 g a day for 6 consecutive postchallenge days did not prevent the development of colds. Nine drug-treated men and 10 controls developed rhinovirus illness. However, the illnesses of the drug-treated men were mild. Rhinorrhea occurred less frequently and was more mild in the drug-treated group. The challenge virus was recovered from 80% of these subjects in both groups, but almost twice the number of challenge viruses were isolated from the controls than from the drug-treated men. The prophylactic DIQA therapy appears to suppress the cold syndrome and to reduce virus excretion, although its effect is marginal. Additional clinical trials are warranted to confirm the antirhinoviral effect of this drug.

Acetamides↗

Cold activation of serum complement in patients with chronic hepatitis C: study on activating pathway and involvement of IgG.

It has been documented that the serum complement activities measured by hemolytic assay (CH50) are decreased after storage of sera at a low temperature in some patients with chronic hepatitis C. However, the mechanism of this phenomenon has not been identified yet. Here, we tried to elucidate factors involved in the cold activation of complement (CAC). To clarify what pathway is activated in CAC, we measured complement cleavage products after cold storage of sera. C4d increased significantly after 12 h-storage at cold temperatures in 5 CAC (+) sera compared with 5 CAC (-) (P < 0.01) and 3 control sera (P < 0.05), while Bb did not increase in any of the groups. In order to determine whether IgG or IgG complex is necessary for CAC, 8 CAC (+) sera were incubated with Protein G Sepharose gel beads, and all of them retained hemolytic activities to some extent after cold storage. Column chromatography through Superose 6HR of CAC-positive serum identified the fractions containing molecules that induced CAC in normal serum, which were depleted by treatment with protein G Sepharose. In conclusion, CAC in hepatitis C seems to occur via a classical or lectin pathway, and the IgG complex produced in hepatitis C virus infection may be an important factor in inducing CAC, a common extrahepatic manifestation of hepatitis C.

Adult↗

Rhinoviruses promote internalisation of Staphylococcus aureus into non-fully permissive cultured pneumocytes.

Respiratory viruses, including rhinoviruses, frequently promote bacterial opportunistic infections, through mechanisms that still deserve to be investigated in detail. This work was aimed at understanding how a viral infection mostly affecting the upper respiratory tract, such as the common cold, can repeatedly promote opportunistic infections in the lower airways, a site where viral replication is limited. The adhesivity and invasivity of Staphylococcus aureus were evaluated, in permissive and non-permissive cells, infected with Rhinovirus-1b. The role of inflammatory cytokines, and of ICAM-1 overexpression in the Rhinovirus-S. aureus cooperation was evaluated. Rhinovirus-1b enhanced the efficiency of internalisation of S. aureus irrespective of cellular permissivity, even when very low viral multiplicities of infection were used. Experiments performed with UV inactivated and heat inactivated viral particles suggested that this enhancement does not depend upon viral replication, but requires viral adhesion. Experimental data suggest that Rhinovirus-1b can significantly increase the ability of S. aureus to internalise into pneumocytes with a mechanism that involves the virus induced release of IL-6 and IL-8, and the overexpression of ICAM-1. Overall data disclose a possible mechanism through which rhinoviruses can promote bacterial infections in the lower respiratory tract.

Epithelial Cells↗

Viral and idiopathic myocarditis in Japan: a questionnaire survey.

In order to study the current clinical status of viral and idiopathic myocarditis in Japan, we conducted a questionnaire survey and collected data for 218 cases from 62 institutions. The diagnosis was based on clinical and laboratory findings alone in 45% of the cases, and it included endomyocardial biopsy in 24% and autopsy in 9% of the patients. Endomyocardial biopsies were available in 40% of the patients; definite cellular infiltrations were identified in half the cases. Regardless of the biopsy findings or availability of biopsy, males predominated in the patient population; the mean age range was 30-39 years for both sexes. Cardiac symptoms and signs were common in addition to "common cold" symptoms; ECG abnormalities, leukocytosis, accelerated erythrocyte sedimentation rate, positive CRP, and increased cardiac enzyme levels were also very common in the acute phase of the disease. Serologic tests for virus titers, performed in 80% of the cases, were positive in 21%. There was no apparent correlation between serologic results and endomyocardial biopsy findings. In this survey, complete recovery occurred in 43%, cure with sequelae in 40%, recurrences in 3%, and death in 13% of the total patient population.

Adolescent↗

An investigation of the possible transmission of Rhinovirus colds through indirect contact.

Rhinovirus was recovered from the fingers of 16 of 38 volunteers and others, who were swabbed during the acute stages of their colds. Very low titres of virus were also recovered from 6 of 40 objects recently handled by infected volunteers, but not from the fingers of 18 non-infected subjects whose flat-mates were shedding virus. When rhinovirus from nasal secretions was dried on skin or other surfaces during laboratory experiments, approximately 40-99% of infectivity was lost. Virus could be transferred from surface to surface by rubbing, the transfer being more efficient if it was carried out while the inoculum was still damp. Volunteers could infect themselves if a moderately heavy dose (88 TCD50) of virus was inoculated on the finger and then rubbed into the conjunctiva or nostril, especially if the inoculum was still damp. From estimates of virus titres in nasal washings and on fingers, and of amounts transferred by rubbing, it was concluded that apread of colds is unlikely to occur via objects contaminated by the hands of the virus-shedder, but that a receipient might pick up enough virus on his fingers by direct contact with heavily infected skin or secretions to constitute a risk of self-inoculation via the conjunctiva or nostril.

Adolescent↗

Stability of lyophilised specimens for the molecular detection of viral DNA/RNA.

BACKGROUND: The range of nucleic acid-based technologies for the molecular detection of pathogens has grown rapidly in recent years. The influx of new testing methods into the clinical laboratory, demands for evaluation and standardisation of methods, interpretation of results and evaluation of laboratory performance have highlighted the need for internal and External Quality Assessment (EQA) systems more than ever before. External Quality Assessment panels demand reproducible, stable specimens of consistent form, suitable for transportation. OBJECTIVES: To determine the stability of freeze-dried viral specimens in terms of molecular detection. STUDY DESIGN: When EQA specimens are prepared, they undergo long-term storage and testing as part of the quality control (QC) process. The frequency and nature of testing is dependent on the resources and methodologies available at the time. A range of virus preparations used for EQA was monitored over a period of months to years in a retrospective study; the available quality monitoring data for the five viruses, including storage temperature and method of detection were analysed. RESULTS: The nucleic acid (DNA or RNA) of the freeze-dried viruses included in the study was readily detectable over a long period of time. Quantitative analysis indicated that detectable concentrations of nucleic acid post-freeze drying were similarly maintained. Storage temperature was an important factor in the stability of HCV, but other viruses were unaffected by storage at different temperatures. CONCLUSIONS: In summary, the molecular detection of nucleic acid (DNA or RNA) in freeze-dried specimens of HSV1, HSV2, HBV, HCV and HIV is possible even after prolonged storage, in some cases at a range of temperatures. Freeze drying allows large-scale production of viral specimens of high quality for EQA, which are stable in varying storage and shipment conditions. Furthermore, detection of each virus was possible with a range of commonly used molecular diagnostic methods.

Cold Temperature↗

Surveillance of community-acquired viral infections due to respiratory viruses in Rhone-Alpes (France) during winter 1994 to 1995.

Nasal swab from patients with acute flu-like illness were evaluated for the presence of respiratory viruses in the Rhone-Alpes region of France from 1 October 1994 through 2 May 1995. The relative frequencies and seasonal distributions of the specific viruses were assessed. In addition, virus type was correlated with specific clinical signs and symptoms. During the study, 962 samples were collected by 75 medical practitioners participating in the Groupe Regional d'Observation de la Grippe surveillance network. One or more viruses were detected from 348 samples (36.1%), including 108 respiratory syncytial virus (RSV), 64 influenza virus A type H3N2, 47 influenza virus B, 64 coronavirus, 35 rhinovirus, 22 adenovirus, 5 enterovirus, and 3 parainfluenza-fluenza strains. There were 16 mixed infections. RSV infections peaked in the early winter, and influenza viruses A and B infections peaked during the late winter and early spring. There were two peaks of coronavirus infections (late fall and late winter). Other viruses were detected at lower levels throughout the study period. Patients from whom adenovirus was isolated were significantly more likely to have a fever of > 39.5 degrees C than were patients with other detectable viruses (P < 0.001). Furthermore, there was a significant correlation between influenza and cough (P < 0.01) and RSV and bronchiolitis (P < .001). Thus, the current study defined the overall and relative frequencies of respiratory virus detection from nasal swab specimens in patients with an acute flu-like illness in the Rhone-Alpes region of France during a 7-month period. Correlation with clinical signs and symptoms and provisional conclusions regarding seasonality were also determined.

Adenovirus Infections, Human↗

Secretory leukocyte protease inhibitor in normal, allergic and virus induced nasal secretions.

Secretory leukocyte protease inhibitor (SLPI) and alpha-1-proteinase inhibitor (alpha-1-PI), both inhibitors of granulocyte elastase, were studied in nasal secretions from healthy persons and from patients with allergic rhinitis and common cold. SLPI and granulocyte elastase were found in all samples, while alpha-1-PI was lacking in several. In all three groups SLPI was found in an active form and in excess of granulocyte elastase, which thus was completely inhibited. The results indicate that SLPI is the main inhibitor in nasal secretions and that alpha-1-PI plays a minor role.

Common Cold↗

Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners.

Fulminant type 1 diabetes is a recently discovered subtype of type 1 diabetes. It is defined as diabetes in which the process of beta-cell destruction and the progression of hyperglycemia and ketoacidosis are extremely rapid. The pathogenesis of this disease remains to be clarified, but the involvement of both genetic background-especially human leukocyte antigen genes-and viruses has been suggested. Fulminant type 1 diabetes has the following clinical characteristics: duration of hyperglycemic symptoms is 4 days on average; there is a high prevalence of preceding common-cold-like and gastrointestinal symptoms; there is a near-normal level of glycated hemoglobin in spite of very high plasma glucose levels associated with ketoacidosis; the disease is sometimes related to pregnancy; and there are increased serum pancreatic enzyme levels, absent C-peptide levels, but virtually no detectable autoantibodies against constituents of pancreatic beta cells. The presence of the above characteristics strongly indicates the diagnosis of fulminant type 1 diabetes. Once the diagnosis of this disease is suspected, treatment of diabetic ketoacidosis must be started immediately, as in all other cases of type 1 diabetes. Otherwise, the death of the patient is likely to occur within 24 h. All medical practitioners must remember that this extremely rapidly progressing type of diabetes does exist, and they must pay special attention not to overlook it.

Acute Disease↗