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Biomedical subjects

K Grünberg

Publications and source records attributed to K Grünberg.

18 recordsLinked to original sources
PubMed2007

Diagnosis and management of pulmonary hypertension over the past 100 years.

Pulmonary hypertension is a rare disease with a poor prognosis. It was first described in the late 19th century as a clinical-pathological syndrome characterised by obstruction of the small pulmonary arteries and right ventricular hypertrophy in patients presenting with severe dyspnoea and cyanosis. After the development of right heart catheterisation in the second half of the 20th century, it was found that many diseases could cause pulmonary hypertension, which is now recognised to be high blood pressure in the arteries that supply the lungs. In the 1960s, an epidemic of pulmonary hypertension caused by appetite suppressants initiated a systematic collection of information on pulmonary hypertension, leading to the first international classification of pulmonary hypertension. Increased understanding of the pathogenesis of the various forms of pulmonary hypertension has led to novel treatments and holds promise for the future.

Appetite Depressants↗
PubMed2003

Interleukin-1beta and interleukin-1ra levels in nasal lavages during experimental rhinovirus infection in asthmatic and non-asthmatic subjects.

BACKGROUND: Exacerbations of asthma are often associated with rhinovirus (RV)-induced common colds. During experimental RV-infection in healthy subjects, increased levels of the pro-inflammatory mediator IL-1beta and the anti-inflammatory IL-1 receptor antagonist (IL-1ra) have been found in nasal lavage. OBJECTIVE: We postulated that the balance between nasal pro- and anti-inflammatory mediator expression is disturbed in asthma, resulting in more extensive inflammation following RV-exposure in asthma. METHODS: We determined IL-1ra, IL-1beta, and IL-8 in nasal lavages (days -2, 3, and 6) of non-asthmatics and asthmatics (with and without pre-treatment with the inhaled steroid budesonide) before and after experimental RV16-infection (days 0 and 1). RESULTS: Following RV16-infection, a significant increase in IL-8 was observed in the placebo- and budesonide-treated asthmatics (P=0.033 and 0.037, respectively), whereas IL-1beta only increased in the two asthma groups combined (P=0.035). A small, but significant, increase in IL-1ra was only observed in the budesonide-treated asthmatics (P=0.047). At baseline, IL-1ra levels were significantly higher in the non-asthmatics than in the placebo-treated asthmatics (P=0.017). CONCLUSION: These results demonstrate differences between non-asthmatic and asthmatic subjects in the basal levels of nasal cytokines and their inhibitors, and in the effect of experimental RV-infection on these levels. The results indicate that RV may enhance inflammation more markedly in asthmatics, and suggest that this may in part be explained by lower IL-1ra levels. In addition, the observation that budesonide-treatment may result in higher nasal IL-1ra levels supports the hypothesis that steroids act in part by increasing the endogenous anti-inflammatory screen.

Asthma↗
PubMed2003

[Magnetosomes as biological model for iron binding: relaxivity determination with MRI].

PURPOSE: In vitro characterization of iron-containing bacterial particles (magnetosomes) as superparamagnetic contrast agents for MRI. MATERIAL AND METHODS: Different concentrations of magnetosomes were examined with a 1.5 T clinical whole-body MR system at 21 degrees C using the transit/receive extremity coil. Both longitudinal and transversal relaxivities (R1 and R2) of the magnetosomes were determined by an inversion recovery snapshot gradient recall echo (IR FLASH) with various inversion times and a multi echo spin echo sequence. Atomic absorption spectrometry (AAS) and electron microscopy were used as reference standard. RESULTS: Longitudinal and transverse relaxivities of the magnetosomes were calculated to be R1 = 7.688 mmol -1 s -1 and R2 = 147.67 mmol -1 s -1, respectively. The corresponding iron concentrations were determined in all dilutions using AAS, while the magnetosomes were morphologically delineated by electron microscopy. CONCLUSION: Magnetosomes represent a new and interesting class of iron-containing contrast agents warranting further evaluation in cellular cultures and animal models. Magnetosomes may be suited for displaying the vector distribution and gene expression of new molecular therapies.

Contrast Media↗
PubMed2002

Rhinovirus infection in nonasthmatic subjects: effects on intrapulmonary airways.

The common cold is a highly prevalent, uncomplicated upper airway disease. However, rhinovirus (RV) infection can lead to exacerbation of asthma, with worsening in airway hyperresponsiveness and bronchial inflammation. The current authors questioned whether such involvement of the intrapulmonary airways is disease specific. Twelve nonatopic, healthy subjects (forced expiratory volume in one second (FEV1) >80% predicted, provocation concentration causing a 20% fall in FEV1 (PC20) >8 mg x mL(-1)) were experimentally infected with RV16. Next to PC20 and the maximal response to methacholine (MFEV1 and MV'40p), the numbers of mucosal inflammatory cells and epithelial intercellular adhesion molecule (ICAM)-1 expression in bronchial biopsies were assessed before and 6 days after RV16 inoculation. RV16 infection induced a small but consistent increase in maximal airway narrowing, without a change in PC20. There was a significant increase in bronchial epithelial ICAM-1 expression after RV16, whereas inflammatory cell counts did not change. Nevertheless, the change in the number of submucosal CD3+ cells was correlated with the change in MV'40p. In conclusion, rhinovirus infection in normal subjects induces a limited, but significant increase in maximal airway narrowing, which is associated with changes in bronchial T-cell numbers. Together with the upregulation of bronchial epithelial intercellular adhesion molecule-1, these findings indicate that, even in healthy subjects, rhinovirus infection affects the intrapulmonary airways.

Adult↗
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↗
PubMed2001

A large gene cluster encoding several magnetosome proteins is conserved in different species of magnetotactic bacteria.

In magnetotactic bacteria, a number of specific proteins are associated with the magnetosome membrane (MM) and may have a crucial role in magnetite biomineralization. We have cloned and sequenced the genes of several of these polypeptides in the magnetotactic bacterium Magnetospirillum gryphiswaldense that could be assigned to two different genomic regions. Except for mamA, none of these genes have been previously reported to be related to magnetosome formation. Homologous genes were found in the genome sequences of M. magnetotacticum and magnetic coccus strain MC-1. The MM proteins identified display homology to tetratricopeptide repeat proteins (MamA), cation diffusion facilitators (MamB), and HtrA-like serine proteases (MamE) or bear no similarity to known proteins (MamC and MamD). A major gene cluster containing several magnetosome genes (including mamA and mamB) was found to be conserved in all three of the strains investigated. The mamAB cluster also contains additional genes that have no known homologs in any nonmagnetic organism, suggesting a specific role in magnetosome formation.

Amino Acid Sequence↗
PubMed2000

Experimental rhinovirus 16 infection increases intercellular adhesion molecule-1 expression in bronchial epithelium of asthmatics regardless of inhaled steroid treatment.

BACKGROUND: Rhinovirus infections in airway epithelial cells in vitro have been shown to upregulate intercellular adhesion molecule-1 (ICAM-1) expression. Epithelial ICAM-1, in its dual role as the major rhinovirus receptor and as adhesion molecule for inflammatory cells may be involved in the pathogenesis of rhinovirus-induced exacerbations of asthma. OBJECTIVE: We aimed to investigate the effect of experimental rhinovirus 16 (RV16) infection on ICAM-1 expression in bronchial mucosal biopsies in asthma. In addition, the effect of 2 weeks pretreatment with inhaled budesonide (800 microg b.d.) on RV16-associated changes in ICAM-1 expression was studied. METHODS: The study had a parallel, placebo-controlled design in 25 steroid-naive nonsmoking atopic asthmatic subjects. After 2 weeks budesonide (BUD) or placebo (PLAC) pretreatment bronchoscopy was performed 2 days before (day -2) and 6 days after (day 6) RV16 inoculation (on days 0 and 1). Immunohistochemical staining for ICAM-1 was performed on snap-frozen bronchial biopsies. ICAM-1 staining intensity on the basal epithelial cells was scored semiquantitatively from 1 (weak) to 3 (intense). Similarly, epithelial intactness was noted (1 = basal cells only, 2 = basal and parabasal cells, 3 = intact epithelium). RESULTS: ICAM-1 scores were not significantly different between the groups at day -2 (P > or = 0.08). Subsequent RV16 infection was associated with a trend towards an increase in ICAM-1 expression in the BUD-group (P = 0.07), whereas the increase was significant in the PLAC-group (P = 0.03). However, the increase was not significantly different between the groups (P = 0.74). Epithelial intactness score was not different between the groups before RV16 infection (P > or = 0.07), and no significant changes were observed in either group (P > or = 0.59). Moreover, ICAM-1 score did not correlate significantly with epithelium score in either group, at any time-point (P > or = 0.27). CONCLUSION: We conclude that an RV16 common cold in atopic asthmatic subjects is associated with increased ICAM-1 expression in the bronchial epithelium, which is not related to epithelial intactness. Glucocorticoid treatment does not appear to prevent the RV16-associated increased ICAM-1 expression. This suggests that other treatment modalities are required to protect against the spreading of infection during rhinovirus-induced exacerbations in asthma.

Administration, Inhalation↗
PubMed1999

Rhinovirus infections: induction and modulation of airways inflammation in asthma.

There is renewed interest in the role of respiratory virus infections in the pathogenesis of asthma and in the development of exacerbations in pre-existing disease. This is due to the availability of new molecular and experimental tools. Circumstantial evidence points towards a potentially causative role as well as to possibly protective effects of certain respiratory viruses in the cause of allergic asthma during early childhood. In addition, it now has become clear that exacerbations of asthma, in children as well as adults, are mostly associated with respiratory virus infections, with a predominant role of the common cold virus: rhinovirus. Careful human in vitro and in vivo experiments have shown that rhinovirus can potentially stimulate bronchial epithelial cells to produce pro-inflammatory chemokines and cytokines, may activate cholinergic- or noncholinergic nerves, increase epithelial-derived nitric oxide synthesis, upregulate local ICAM-1 expression, and can lead to nonspecific T-cell responses and/or virus-specific T-cell proliferation. Experimental rhinovirus infections in patients with asthma demonstrate features of exacerbation, such as lower airway symptoms, variable airways obstruction, and bronchial hyperresponsiveness, the latter being associated with eosinophil counts and eosinophilic cationic protein levels in induced sputum. This suggests that multiple cellular pathways can be involved in rhinovirus-induced asthma exacerbations. It is still unknown whether these mechanisms are a distinguishing characteristic of asthma. Because of the limited effects of inhaled steroids during asthma exacerbations, new therapeutic interventions need to be developed based on the increasing pathophysiological knowledge about the role of viruses in asthma.

Adult↗
PubMed1999

Experimental rhinovirus 16 infection causes variable airway obstruction in subjects with atopic asthma.

Exacerbations of asthma are often associated with rhinovirus infections. However, it has not been investigated whether rhinovirus infection can induce variable airway obstruction in asthma. We examined the effect of experimental rhinovirus 16 (RV16) infection on daily home recordings of FEV(1) in 27 subjects (nonsmoking, atopic, mildly asthmatic) who participated in a parallel placebo-controlled study. The subjects used a microspirometer to record FEV(1) three times daily from 4 d before until 10 d after RV16 (n = 19) or placebo (n = 8) inoculation. In addition, symptoms of asthma and symptoms of common cold were scored. Airway hyperresponsiveness to histamine was measured 3 d before and on Days 4 and 11 after RV16/placebo administration. Home recordings of FEV(1) decreased significantly after RV16 infection, reaching a minimum 2 d after inoculation (ANOVA, p </= 0.005), which was significantly different from placebo (p </= 0.004). In the RV16 group the lowest FEV(1) (expressed as a percentage of personal best) during Days 0-3 after infection (mean +/- SEM: 78.7 +/- 2.6% versus baseline: 85.6 +/- 1.2%, p = 0.008) correlated significantly with the cold score (r = -0.47, p = 0.04), asthma score (r = -0.47, p = 0.04), and with the decrease in airway hyperresponsiveness on Day 4 as compared with baseline (r = 0.50, p = 0.03). We conclude that experimental RV16 infection augments variable airway obstruction in subjects with asthma. This favors a causative role for rhinovirus colds in asthma exacerbations, and is in keeping with rhinovirus-induced worsening of airway inflammation.

Adolescent↗
PubMed1998

A rebreathing method to determine carbon monoxide diffusing capacity in children: reference values for 6- to 18-year-olds [corrected] and validation in adult volunteers.

The diffusing capacity of carbon monoxide (D(L,CO)) and its value normalized to alveolar volume (D(L,CO)/V(A)) are usually estimated with the single breath method at total lung capacity (TLC). Severely ill patients and small children are not able to deliver a satisfactory vital capacity (VC) or hold their breath for 10 s at TLC. The aim of this study was to develop a rebreathing procedure in which diffusing capacity can be determined during spontaneous tidal breathing. The conventional rebreathing method during hyperventilation was modified so that rebreathing volume and gas concentrations were kept constant by CO2 absorption and O2 supplementation. In adult healthy volunteers and in patients who were able to perform both tests, the diffusion indices obtained with this rebreathing method during resting ventilation were compared with those obtained by the single breath method. Predicted (reference) values for rebreathing D(L,CO) and D(L,CO)/V(A) for children were determined. D(L,CO)/V(A) decreased with alveolar volume (V(A)) and increased with alveolar ventilation (V'(A)). In adults at V'(A) above 35 L x min(-1) rebreathing D(L,CO)/V(A) was similar to single breath D(L,CO)/V(A) at similar alveolar volumes. The D(L,CO)/V(A) relative to their corresponding reference values were the same for both methods in adult patients, irrespective of ventilation distribution disturbances. In children the newly described diffusing capacity obtained by the rebreathing method during resting ventilation can serve as a valuable index to assess and follow a diffusion disorder.

Absorption↗
PubMed1998

Cytokine release and its modulation by dexamethasone in whole blood following exercise.

Glucocorticoids (GC) play an important role in the treatment of inflammatory diseases like asthma. However, in selected patients a relative resistance to GC has been reported. Recently, it has been suggested that GC sensitivity of peripheral blood leucocytes may be regulated in a dynamic fashion during exercise, in association with activation of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of the present study was to explore changes in the GC sensitivity of cytokine production by leucocytes following strenuous exercise by well trained oarsmen. These changes were studied using lipopolysaccharide (LPS)-induced and anti-CD2/anti-CD28 MoAb-stimulated cytokine release in whole blood and its modulation by dexamethasone. Following exercise, significant decreases in LPS-induced release of IL-6, tumour necrosis factor-alpha (TNF-alpha) and IL-10 and anti-CD2/anti-CD28 MoAb-stimulated secretion of interferon-gamma (IFN-gamma) were observed. In addition, the inhibitory effect of dexamethasone on both IL-6 and TNF-alpha secretion was significantly reduced following exercise, whereas that on IL-10 and IFN-gamma release was not affected. These exercise-induced changes were accompanied by activation of the HPA axis, as indicated by an increase in circulating adrenocorticotropic hormone (ACTH) levels immediately following exercise. The results from the present study suggest that GC sensitivity of whole blood cytokine release can be regulated in a dynamic fashion and that this can be assessed using an ex vivo stimulation assay. Moreover, since dexamethasone responsiveness of anti-CD2/anti-CD28 MoAb-induced IFN-gamma secretion in whole blood is not affected by exercise, it may suggest that exercise differentially affects monocytes and lymphocytes. The dynamic regulation of steroid responsiveness of leucocytes, as observed in the present study, could have important consequences for the effectiveness of GC treatment in inflammatory diseases.

Adolescent↗
PubMed1998

Relationship between exhaled nitric oxide and airway hyperresponsiveness following experimental rhinovirus infection in asthmatic subjects.

Exhaled nitric oxide (NO) is elevated in asthmatics, and varies with disease severity. We postulated that a respiratory virus infection increases exhaled NO levels in asthma, and examined the relationship between the virus-induced changes in exhaled NO and in airway hyperresponsiveness to histamine. In a parallel study, seven patients underwent experimental rhinovirus 16 (RV16) inoculation at days 0 and 1, whilst seven patients received placebo. Exhaled NO was measured at baseline (day 0) and at days 1, 2 and 3 after inoculation. Histamine challenges were performed prior to (day -7) and after inoculation (day 3), and were expressed as provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). Following RV16 infection there was a significant increase in NO at days 2 and 3 as compared to baseline (median change (range): 4.2 (7.5) parts per billion (ppb), p=0.03, and 3.0 (10.1) ppb, p=0.02, respectively). Furthermore, PC20 decreased significantly following RV16 infection (mean+/-SD change in doubling dose: -0.65+/-0.54, p=0.02), whereas PC20 did not change in the placebo group (p=0.1). There was a significant correlation between the RV16-induced changes in exhaled NO levels at day 2 and the accompanying changes in PC20 at day 3 (rank correlation coefficient (rs): 0.86, p=0.01). Hence, the greater the increase in exhaled NO, the smaller the decrease in PC20. We conclude that rhinovirus infection increases exhaled nitric oxide levels in asthmatics, and that this increase is inversely associated with worsening of airway hyperresponsiveness to histamine. These results suggest that viral induction of nitric oxide synthase within the airways may play a protective role in exacerbations of asthma.

Adult↗
PubMed1998

["Repeating" the transference? The central relationship conflict topic of the 290th session--questions, problems, results].

The following text sums up the results of an examination of a therapeutic session in which a psychoanalyst treated a patient suffering from neurotic depression. We employed the CCRT method which was applied at various levels of abstraction and in two steps of evaluation. The standard evaluation procedure allows for both a more thorough evaluation of "self-relationship episodes" and episodes involving other objects. An integration of "tailor-made" formulations allowed us to analyse another set of "relationship-patterns": namely, those which, in contrast to those most often found in conflict themes, contain positive traits. These results were then discussed clinically to examine these in light of the therapeutic conception of depression. In this context, the question arose as to whether the classic CCRT method can be fruitfully applied in long-term analysis and if this notion should be modified in order to examine the analysis of depression more effectively. A first attempt at such a modification was undertaken in the hope it would allow us to evaluate both the relevance of meaning passages contained in the clinical data and the visible processes of change.

Adjustment Disorders↗
PubMed1997

Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo.

Disturbance of the balance between excitatory and inhibitory activity of the airway sensory nerves has been implicated in asthma pathogenesis, particularly during exacerbations of the disease. The objective of this study was to examine the effect of experimental rhinovirus 16 (RV16) infection on airway responsiveness to bradykinin, a potent sensory nerve stimulus, in asthma. Thirteen atopic, mildly asthmatic subjects participated in a parallel, placebo-controlled study. A total dose of 2.6 to 5.6 x 10(4) TCID50 RV16 (n = 7) or its diluent (n = 6) was inoculated on 2 consecutive days (Days 0 and 1). Histamine and bradykinin challenges were performed before (Days-7 and-6) and after (Days 3 and 4) inoculation. The response was measured by FEV1 and partial flow-volume curves, and it was expressed as PC20FEV1 and PC40V40p, respectively (changes expressed in doubling dose: DD). Before inoculation, PC20FEV1 and PC40V40p to histamine were not significantly different between the groups (p > or = 0.22), whereas PC20FEV1 and PC40V40p to bradykinin tended to be higher in the RV16 group (p = 0.11 and p = 0.06, respectively). PC20FEV1 and PC40V40p to histamine decreased significantly in the RV16 group (mean change +/- SEM: -0.65 +/- 0.20 DD, p = 0.02 and -0.98 +/- 0.28 DD, p = 0.01, respectively), but not in the placebo group (p > or = 0.26). PC40V40p to bradykinin increased significantly in the placebo group (+2.46 +/- 0.92 DD, p = 0.04), with a similar trend for PC20FEV1 (+1.50 +/- 0.62 DD, p = 0.06), whereas there were no significant changes in the RV16 group (p > or = 0.77). These changes in PC40V40p to histamine and bradykinin were significantly different between the groups (p = 0.02). We conclude that repeated bradykinin challenge over a 10-d interval induces tachyphylaxis in asthmatic subjects in vivo and that experimental RV16 infection abolishes such tachyphylaxis to bradykinin while it enhances airway responsiveness to histamine. These results do not favor a predominant role of airway sensory nerves in rhinovirus-induced exacerbations of asthma.

Adult↗
PubMed1997

Experimental rhinovirus 16 infection. Effects on cell differentials and soluble markers in sputum in asthmatic subjects.

Asthma exacerbations are often associated with respiratory virus infections, particularly with rhinovirus. In the present study we investigated the effect of experimental rhinovirus 16 (RV16) infection on airway inflammation as assessed by analysis of hypertonic saline-induced sputum. Twenty-seven nonsmoking atopic, mildly asthmatic subjects participated in a placebo-controlled parallel study. RV16 (n = 19) or its diluent (n = 8) was nasally administered. Sputum inductions were performed at entry and on Days 2 and 9 after inoculation, and airway responsiveness to histamine (PC20) was measured on Days 4 and 11. Cell differentials and levels of albumin, eosinophil cationic protein (ECP), IL-8, and IL-6 were determined. The cellular origin of IL-8 was investigated by intracellular staining. RV infection was confirmed by culture and/or by antibody titer rise in each of the RV16-treated subjects. There were no significant changes in the sputum differentials of nonsquamous cells (MANOVA, p > or = 0.40). In the RV16 group, there was a significant increase in the levels of ECP, IL-8, and IL-6 at Day 2 after infection (p < 0.05), whereas the albumin levels did not change (p = 0.82). The levels of IL-8 and IL-6 remained elevated for as long as 9 d after infection (p < 0.05). The increase in the percentage of IL-8 positive cells at Day 2 after infection could be attributed to the increase in IL-8 positive neutrophils (p < 0.02). There was a significant decrease in PC20 at Day 4 (p = 0.02), which was no longer significant at Day 11 (p = 0.19). The decrease in PC20 correlated significantly with the increase in ECP in the first week (r = -0.60) and with the change in the percentage eosinophils in the second week after inoculation (r = -0.58). We conclude that experimental RV16 infection in atopic asthmatic subjects increases airway hyperresponsiveness in conjunction with augmented airway inflammation, as reflected by an increase in ECP, IL-8, and IL-6 in sputum. Our results suggest that the RV16-enhanced airway hyperresponsiveness is associated with eosinophilic inflammation.

Adolescent↗
PubMed1997

Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo.

BACKGROUND: Asthma exacerbations are closely associated with respiratory virus infections. However, the pathophysiological consequences of such infections in asthma are largely unclear. OBJECTIVE: To examine the effect of rhinovirus 16 (RV16) infection on airway hypersensitivity to histamine, and on interleukin-8 (IL-8) in nasal lavage. METHODS: Twenty-seven non-smoking atopic, mildly asthmatic subjects participated in a placebo-controlled, parallel study. A dose of 0.5-2.9 x 10(4) TCID50 RV16 or placebo was nasally administered. Cold symptoms were recorded by questionnaire throughout the study. Histamine challenges were performed at entry, and on days 4 and 11 after inoculation. Nasal lavages were obtained at entry, and on days 2 and 9. The response to histamine was measured by PC20 (changes expressed as doubling doses: DD) IL-8 levels were obtained by ELISA, and were expressed in ng/ml. RESULTS: RV infection was confirmed by culture of nasal lavage and/or by antibody titre rise in each of the RV16-treated subjects. Among the 19 RV 16-treated subjects, eight developed severe cold symptoms. Baseline FEV1, did not change significantly during the study in either treatment group (P = 0.99). However, in the RV16-treated subjects there was a decrease in PC20 at day 4, which was most pronounced in those with a severe cold (mean change +/- SEM: -1.14 +/- 0.28 DD, P = 0.01). In addition, IL-8 levels increased in the RV16 group at days 2 and 9 (P < 0.001). The increase in nasal IL-8 at day 2 correlated significantly with the change in PC20 at day 4 (r = -0.48, P = 0.04). CONCLUSION: We conclude that the severity of cold, as induced by experimental RV16 infection, is a determinant of the increase in airway hypersensitivity to histamine in patients with asthma. Our results suggest that this may be mediated by an inflammatory mechanism, involving the release of chemokines such as IL-8.

Adolescent↗
PubMed1996

Pulmonary diffusing capacity at reduced alveolar volumes in children.

The diffusing capacity, when normalized per liter of alveolar volume (DL,CO/VA) decreases in normal adults, whereas their total diffusing capacity (DL,CO) increases as alveolar volume (VA) increases. We studied these relationships in a group of normal children below 20 years of age. Diffusion variables were determined using the single breath technique. The effects of sex, age, and height on these relationships were estimated. DL,CO increased and DL,CO/VA decreased as alveolar volume increased. DL,CO and DL,CO/VA reference values at total lung capacity (TLC) appeared to be comparable to reference values at TLC in the literature. Reference values of DL,CO and DL,CO/VA derived from measurements at various alveolar volumes also predict similar values at TLC. The advantage of our reference equations is their applicability to patients with restrictive lung disease. Actual DL,CO/VA can be compared with reference DL,CO/VA at actual (restrictive) TLC instead of reference DL,CO/VA at reference TLC. This comparison extends the evaluation of a diffusion disorder.

Adolescent↗