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Biomedical subjects

C R Dick

Publications and source records attributed to C R Dick.

10 recordsLinked to original sources
PubMed2001

Rhinovirus-induced airway inflammation in asthma: effect of treatment with inhaled corticosteroids before and during experimental infection.

Asthma exacerbations are frequently linked to rhinovirus infections. However, the associated inflammatory pathways are poorly understood, and treatment of exacerbations is often unsatisfactory. In the present study we investigated whether antiinflammatory treatment with inhaled corticosteroids prevents any rhinovirus-induced worsening of lower airway inflammation. To that end, we selected 25 atopic patients with mild asthma who underwent experimental rhinovirus 16 (RV16) infection, while receiving double-blind, placebo-controlled treatment with the inhaled corticosteroid budesonide (800 microg twice a day) throughout the study period, starting 2 wk before infection. We assessed inflammatory cell numbers in the bronchial mucosa as obtained by bronchial biopsies 2 d before and 6 d after RV16 infection, and analyzed those in relation to cold symptoms, changes in blood leukocyte counts, airway obstruction, and airway hyperresponsiveness. RV16 colds induced an increase in CD3(+) cells in the lamina propria (p = 0.03) and tended to decrease the numbers of epithelial eosinophils (p = 0.06) in both groups analyzed as a whole. The T cell accumulation was positively associated with cold symptoms. Budesonide pretreatment improved airway hyperresponsiveness (p = 0.02) and eosinophilic airways inflammation (p = 0.04). Yet it did not significantly affect the RV16-associated changes in the numbers of any of the inflammatory cell types. We conclude that RV16 infection by itself induces only subtle worsening of airway inflammation in asthma, which is not improved (or worsened) by inhaled corticosteroids. The latter finding is in keeping with the limited protection of inhaled corticosteroids against acute asthma exacerbations.

Administration, Inhalation↗
PubMed2000

Rhinovirus-induced PBMC responses and outcome of experimental infection in allergic subjects.

BACKGROUND: The immune response to rhinovirus (RV) infections is considered to contribute to upper respiratory symptoms and may also be an important contributor to lower airway dysfunction in patients with asthma. OBJECTIVE: This study was conducted to determine the relationship of RV-specific responses in PBMCs to the outcome of experimentally induced infection with RV16. METHODS: Twenty-two subjects with either allergic rhinitis or asthma were inoculated with RV16: virus-induced proliferation and cytokine production were determined on PBMCs obtained before and then again 7 and 28 days after inoculation. RESULTS: Several subjects had proliferative responses to RV16 before inoculation, and precold RV-specific proliferative responses were inversely correlated (r(s) = -0.62, P <. 005) with RV shedding after inoculation. In addition, there was a negative correlation (r(s) = -0.58, P = 0.01) between precold RV-induced IFN-gamma secretion ex vivo and peak RV shedding during the cold. CONCLUSIONS: Certain RV-specific lymphocyte responses before the cold (vigorous proliferation or IFN-gamma secretion) were associated with reduced viral shedding after inoculation. These findings suggest that variations in mononuclear cell responses to RV could contribute to the individual variability in viral shedding during experimentally induced, and perhaps naturally acquired, RV infections in subjects with respiratory allergy or asthma.

Adolescent↗
PubMed2000

The effect of an experimental rhinovirus 16 infection on bronchial lavage neutrophils.

BACKGROUND: Viral respiratory tract infections are the most frequent cause of asthma exacerbations. Of the respiratory viruses associated with these exacerbations, rhinovirus (RV) is the most common. It is proposed that these RV infections may enhance airway inflammation and thus provoke asthma. OBJECTIVE: It is our hypothesis that RV infections generate nasal proinflammatory mediators that are associated with an initial increase in circulating leukocytes and may contribute to later development of neutrophilic airway inflammation. METHODS: To evaluate this hypothesis, subjects with a history of allergic asthma were experimentally inoculated with strain 16 RV (RV16). The effect of this experimental infection was evaluated on circulating leukocytes, nasal-derived mediators, and markers of bronchial inflammation that were obtained by bronchoscopy and lavage. RESULTS: RV16 inoculation was associated with an initial increase in circulating neutrophils. Paralleling these acute changes in circulating neutrophils was an increase in nasal concentrations of IL-8 and granulocyte-colony-stimulating factor (G-CSF). The RV16-associated changes in circulating and nasal G-CSF correlated with increases in peripheral blood neutrophils (r(s) = 0.874, P <. 001 and r(s) = 0.898, P <.001, respectively). Bronchial lavage samples showed no increase in neutrophils 48 hours after RV16 inoculation; however, 96 hours after RV inoculation there was a significant increase in bronchial neutrophils compared with preinoculation values. CONCLUSIONS: These results suggest that the production of nasal mediators associated with the RV infection, particularly G-CSF, may be important to the eventual development of neutrophilic bronchial inflammation and thus contribute to asthma exacerbations.

Adult↗
PubMed1997

O2-induced change in ventilation and ventilatory drive in COPD.

We examined the role of respiratory control during O2-induced hypercarbia in patients with chronic obstructive pulmonary disease (COPD), by comparing the observed change in ventilation (delta VEobs) with the delta VE predicted (delta VEpred) from the patients' ventilatory drive and the O2-induced delta PaCO2 and delta SaO2. Eleven stable hypoxemic COPD patients (mean +/- SD: FEV1 = 1.00 +/- 0.25 L, FVC = 2.33 +/- 0.38 L; room air PaCO2 = 52.7 +/- 7.9 mm Hg, SaO2 87.7 +/- 5.1%) were studied. Using standard rebreathing methods, we measured the ventilatory responses to hypercapnia (delta VE/PCO2 = 0.76 +/- 0.55 L/min/mm Hg) and to hypoxia (delta VE/delta SaO2 = -0.74 +/- 0.31 L/min/%). After breathing 100% O2 for 15 min, the mean delta VEobs was -0.08 +/- 0.62 (SEM) L/min (p = NS), the delta SaO2 was 7.6 +/- 3.6% (p < 0.001), and the delta PaCO2 was 6.6 +/- 3.3 mm Hg (p < 0.001). The delta VEpred was expressed as the sum of a decrease in ventilation due to suppression of hypoxic drive [calculated as the product (delta VE/SaO2) x delta SaO2] and an increase in ventilation due to the O2-induced hypercarbia [calculated as the production (delta VE/delta PCO2) x delta PaCO2]. The mean delta VEpred [-0.96 +/- 0.68 (SEM)] did not differ significantly from mean delta VEobs. We conclude that the O2-induced delta VEobs is equal to that expected from the ventilatory drives and the changes in PaCO2 and SaO2; and that O2-induced hypercarbia does not indicate a failure of respiratory control mechanisms in the maintenance of PaCO2 homeostasis.

Dose-Response Relationship, Drug↗
PubMed1996

Patient-ventilator interactions.

Patient-ventilator synchrony is important in the management of the ventilator-dependent patient. Factors inherent to the patient and the ventilator influence patient-ventilator synchrony. Detection of patient-ventilator synchrony may require monitoring of airway pressure and flow waveforms.

Humans↗
PubMed1984

Short-duration exposure and the transmission of rhinoviral colds.

Transmission of infection with rhinovirus type 55 was attempted under natural circumstances of interaction among 26 experimentally infected donors and 33 antibody-free (titer, less than 1:3) recipients. In a total of three experiments, only two recipients (6%) became infected. In the first experiment no transmissions from five donors to nine recipients occurred after 2-3 hr of loud vocalization and card playing in a small room. In the second experiment a cold was transmitted to one (9%) of 11 recipients living in dormitory rooms for 36 hr in groups consisting chiefly of two donors and two recipients. In the third experiment one (8%) of 13 recipients was infected after kissing an infected donor. In studies with rhinovirus type 16, the 50% human infectious dose was found to be 0.28 TCID50 (50% tissue culture infectious dose) in the nose, 2,260 TCID50 on the tongue, and 11,000 TCID50 on the external nares. Rhinoviral infections are difficult to transmit by short-term natural exposure, perhaps because the agent must be present in overwhelming numbers to reach susceptible mucosal cells.

Adolescent↗
PubMed1976

Transmission of experimental rhinovirus colds in volunteer married couples.

Communicability of rhinovirus type 16 or type 55 was studied in 24 childless couples; on partner (the donor) was infected with laboratory-grown virus. Initially, both partners lacked antibody to the challenge agent. Rates of transmission between partners were 41% and 33% for type 16 and type 55, respectively. These rates are similar to those determined in epidemiologic studies of natural rhinovirus infection. Although the mucosa of the anterior nares was shown to be highly susceptible to infection (less than one 50% tissue culture infective dose [TCID50]), transmission rarely occurred unless (1) at least 1,000 TCID50 of virus was recovered from the donor's nasal washing, (2) the donor had virus on his hands and anterior nares, (3) he was at least moderately symptomatic, and (4) he spent many hours with his spouse. Since person-to-person transfer of rhinovirus was so dependent upon time spent together and shedding of large amounts of virus by the donor, it seems possible that the chain of infection could be interrupted by environmental manipulation.

Clinical Trials as Topic↗
PubMed1975

Attenuated influenza A vaccine (Alice) in an adult population: vaccine-related illness, serum and nasal antibody production, and intrafamily transmission.

Ninety-five healthy adults, ages 18 to 56 years, received two intranasal doses, 2 weeks apart, of a live, attenuated, influenza type A (H3N2) vaccine (an inhibitor-resistant recombinant strain of A/England/42/72 named "Alice"). Ninety-two persons were given placebos similarly. Ninety-three percent of 68 subjects with initial serum hemagglutination-inhibition (HI) titers of greater than or equal to 1:40 to influenza A (H3N2) had a fourfold or greater antibody increase in postvaccination sera. Forty-four percent of 27 subjects with an initial HI titer of greater than or equal to 1:80 had similar increases. Overall, 77% of vaccinees had fourfold or greater antibody titer increases. Vaccinees had geometric mean serum HI titers (GMT) of 1:26, 1:123, and 1:166 at 0, 14, and 30 days, respectively. The GMTs for placebos were 1:21, 1:22, and 1:21. Thirty-five vaccinees were examined for both serum and nasal antibody; 89% had significant increases in one or both. Nasal antibody response was directly related to the level of initial serum HI titer in that 83% of 12 persons with prevaccination HI titers of 1:80 greater than or equal to 1:80 showed significant nasal antibody rises, whereas only 61% of the remaining 23 subjects with prevaccination HI titers of less than or equal to 1:40 did so. The number and severity of clinical signs and symptoms reported by vaccinees and placebos did not differ significantly. The greatest differences noted between groups were for nasal congestion on days 0 to 6 (8.3%) and rhinitis on days 14 to 20 (5.9%). Four vaccinees shed Alice after primary vaccination, but viral titers were low (10 to 100 tissue culture-infective doses/ml). One member in each of 15 cohabiting male-female couples received Alice while the other received a placebo; one of the placebo members had significant increases in serum and nasal antibody, indicating a possible transmission.

Administration, Intranasal↗