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Biomedical subjects

Ronald Dahl

Publications and source records attributed to Ronald Dahl.

At least 19 recordsLinked to original sources
PubMed2006

Allergy in bakers' apprentices and factors associated to non-participation in a cohort study of allergic sensitization.

OBJECTIVE: To describe the prevalence of atopy and respiratory symptoms among baker apprentices at the start of the education and factors associated with non-participation in the study. METHODS: A total of 346 students, 22.1(0.6) years of age, mean (SD), from the food production programme of technical colleges in Denmark were invited to participate in a 3 year study. Of the students, 187 agreed to participate and filled in a physician-administered questionnaire. The presence of atopy was determined by skin prick test (SPT) and serum allergen specific IgE (SpIgE). Bronchial hyper responsiveness to methacholine (PD(20) <or= 1,440 microg) was determined. RESULTS: Prevalence of atopy was 32%. The prevalence of symptoms from the lungs and nose was 19.8 and 25.5%, respectively. Significantly, more SPT reactions were seen in males compared to females (39 vs. 22%, P < 0.05). Sensitization towards flour was significantly more frequent if determined as SpIgE (7.3%) compared to SPT (0.5%). We found a positive association between atopy and lung symptoms OR 6.1 (2.8-13.2 SD) and nasal symptoms OR 3.7 (1.8-7.5 SD). The major reason for non-participation was fear of blood sampling (25.5%). CONCLUSION: The prevalence of atopy in bakers' apprentices was of the same magnitude in the general Danish population. Significantly, more male bakers' apprentices had atopy. This finding has major impact on the diagnostic procedures of occupational allergy in bakery workers emphasizing the need for standardization of the clinical tests. The main reasons for non-participation were, fear of blood-sampling (57%) and the 3 years commitment to the follow-up study (39%).

Adolescent↗
PubMed2006

Response of respiratory flour allergics in an ingested flour challenge may involve plasmacytoid dendritic cells, CD25+ and CD152+ T cells.

BACKGROUND: A number of occupational respiratory allergens are food related, and little is known about the responses these allergens elicit in sensitized persons that ingest them. METHODS: Nine respiratory flour-allergic volunteers were exposed in a double-blind placebo-controlled food challenge with flour. Responses were monitored by spirometry, acoustic rhinometry, determination of urinary methyl histamine and tryptase and flow cytometric evaluation of basophil, dendritic and T cell numbers and markers. RESULTS: Significant increases in serum tryptase (compared with placebo post-exposure levels) and methyl histamine and a coordinated decrease in blood basophils and nasal volume after ingestion of allergen compared with placebo suggest an allergic response to ingested allergen. There was no change in forced expiratory volume in 1 s. The number of blood plasmacytoid dendritic cells (DC), but not of myeloid DC, decreased after exposure (p = 0.001). DC HLA DR was reduced after both exposures (p < 0.001). Expression of CXCR4 on DC was reduced after allergen (p = 0.033) but not after placebo exposure. CD4+ T cell expression of CD25 was elevated after placebo (p = 0.021) but reduced after allergen provocation. The reduction in CD25 expression after allergen compared with placebo was significant (p = 0.024). CD152 was downregulated on these cells after allergen (p = 0.039) but less so after placebo exposure. CONCLUSION: Persons with respiratory allergy respond after ingestion of the relevant allergen. Response to this allergen challenge may selectively recruit plasmacytoid DC through CXCR4 and T cells expressing CD25 and CD152, which may be a regulatory phenotype.

Adult↗
PubMed2006

EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma.

OBJECTIVES: This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids. METHODS: The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group. RESULTS: The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated. CONCLUSIONS: Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.

Administration, Inhalation↗
PubMed2006

[General practitioners' attitudes towards the diagnosis of lung cancer and the diagnostic organisation].

INTRODUCTION: The aim of this study was to determine whether there is a nihilistic attitude towards diagnosing lung cancer among Danish general practitioners (GPs) and to obtain the GPs' evaluation of the present approach to lung cancer diagnosis. MATERIALS AND METHODS: A questionnaire was sent to 1,186 randomly selected GPs. Most of the questions addressed the possibilities of improving primary prevention, GPs' attitudes towards diagnosing lung cancer, their opinions about waiting times and their clinical practice. RESULTS: A total of 848 (71%) completed the questionnaire. Only 12% agreed with the statement that the prognosis for lung cancer is so unfavourable that there is no hurry to diagnose the disease, while 22% agreed to the statement that diagnostic delay rarely means anything for the prognosis. About half of the GPs found the diagnostic period too long. There were, however, wide variations among the different counties in Denmark. The majority of GPs followed the recommendations of the Danish Lung Cancer Group for diagnosing lung cancer, especially the elderly GPs, who were also more inclined to make follow-up appointments after lung infections. More than one in every four practitioners was reluctant to use the word "cancer" in referrals to hospitals or for investigation. CONCLUSION: The study showed that Danish GPs do not have a nihilistic attitude towards diagnosing lung cancer and that elderly practitioners are more careful about diagnosing lung cancer. GPs' satisfaction with waiting times varies widely among the different counties in Denmark. Many practitioners were reluctant to use the word "cancer" in referrals.

Adult↗
PubMed2006

Systemic side effects of inhaled corticosteroids in patients with asthma.

Asthma is a complex disease of the respiratory tract associated with chronic inflammation in which an intricate network of cells and cellular factors plays a major role. Asthma is one of the most common chronic diseases, with an estimated 300 million cases worldwide, imposing a considerable burden on society in morbidity, quality of life, and healthcare costs. Inhaled corticosteroids (ICSs) form the gold standard, first-line therapy in the effective management of persistent asthma and reduce morbidity and mortality from asthma. However, long-term use of high-dose ICS therapy has potential to cause systemic side effects-impaired growth in children, decreased bone mineral density, skin thinning and bruising, and cataracts. Hypothalamic-pituitary-adrenal-axis suppression, measured by serum or urine cortisol decrease, correlates with the occurrence of systemic side effects of high-dose ICSs. Therefore, cortisol may be a relevant surrogate marker to identify the potential for adverse effects from ICS therapy. Ciclesonide is a new generation ICS with demonstrable safety and efficacy in the treatment of asthma. The unique pharmacologic characteristics of ciclesonide, such as reduced local adverse effects, lack of cortisol suppression, and the option for once-daily dosing, may improve compliance with therapy and allow long-term use of ICSs without fear of systemic adverse effects.

Administration, Inhalation↗
PubMed2006

Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis.

BACKGROUND: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. OBJECTIVE: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abelló, Hørsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. METHODS: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. RESULTS: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. CONCLUSION: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. CLINICAL IMPLICATIONS: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use.

Administration, Sublingual↗
PubMed2006

Delay in diagnosis of lung cancer in general practice.

BACKGROUND: Lung cancer is a common cancer disease; nevertheless, in Denmark a GP only sees one new case of lung cancer per year. The core symptoms of lung cancer, cough and dyspnoea, are on the other hand very common in general practice. This represents a challenge to the diagnostic process and increases the risk of diagnostic delay. AIM: To explore diagnostic delay in primary health care among patients with lung cancer. DESIGN OF STUDY: A population based observational case series of 84 lung cancer patients' delay. SETTING: The County of Aarhus, Denmark. METHOD: From county-based registers of all histological and cytological tests we identified all patients in the County of Aarhus with lung cancer diagnosed during a 6 month period in 2003. Inclusion was verified by contacting the departments involved in the treatment of lung cancer. Data were based on telephone interviews with patients' GPs. A review of delay was made starting with the first symptom until referral to secondary care. RESULTS: The overall median delay in primary health care was 32.5 days (interquartile interval (IQI) = 12-68 days). One-third of the patients were referred to the diagnostic investigation after their first consultation. Important reasons for delay in primary care were: symptoms not related to the lungs, chest X-ray without suspicion of cancer, comorbidity, waiting times for investigations and lack of explicit follow-up appointment. Prolonged delay was often due to a combination of these factors. CONCLUSION: When diagnosing lung cancer, it is important that GPs are aware of the low sensitivity of chest X-ray. Shorter waiting times for investigations could reduce delay considerably.

Adult↗
PubMed2005

A single exposure to organic dust of non-naïve non-exposed volunteers induces long-lasting symptoms of endotoxin tolerance.

BACKGROUND: Work with occupational levels of organic dust is associated with a chronic inflammatory response that must somehow be controlled. Endotoxin tolerance has previously been described in vitro and animal studies as a mechanism that modifies the threshold at which response occurs. OBJECTIVE: We investigated the response of non-naïve, currently non-exposed persons to a single exposure of organic dust in a swine confinement building. METHODS: We exposed 16 non-naïve persons in a swine confinement building with low-to-moderate representative levels of organic dust and characterized their acute immune response. RESULTS: Under work-like 3-hour exposure conditions, non-naïve volunteers developed an inflammatory response documented by an increase in interleukin-6 (IL-6) in bronchoalveolar lavage (BAL) from 3.1 to 6.1 pg/ml and visual indices of bronchial inflammation. Similarly, serum IL-6 increased with a peak 3 h after exposure. Tumor necrosis factor (TNF)-alpha was not detected in BAL, and serum TNF-alpha was reduced from 3.7 pg/ml at baseline to less than 2 pg/ml within 3 h after exposure, and remained decreased until 2 weeks after exposure. This is a cardinal marker for immune suppression which was confirmed by other markers: reduction in HLA-DR expression on alveolar macrophages and CD14 expression on blood monocytes. CONCLUSION: We report findings that suggest that long-lasting endotoxin tolerance and immune suppression may be induced by a brief exposure to organic dust concentrations in the medium-low range of occupational levels.

Adult↗
PubMed2005

Lysis with Saponin improves detection of the response through CD203c and CD63 in the basophil activation test after crosslinking of the high affinity IgE receptor FcepsilonRI.

BACKGROUND: The basophil activation test (BAT), in which translocation of markers to the surface of blood basophils is measured in response to allergen by flow cytometry, is a rapid assay that is gaining popularity. Two markers are currently being evaluated for the BAT; CD63 and the lineage-specific CD203c. In a recent report, detection of CD203c after lysis with Saponin was shown to be superior to detection of CD63 after lysis with formic acid. We wanted to compare a) lysis with formic acid and lysis with Saponin, b) the response through CD203c and CD63, and c) the definition 10% activated cells above background with the probability binning metric T(chi) > 4, on sets of data generated with blood basophils stimulated with varying concentrations of anti-FcepsilonRI antibody. METHODS: Blood from volunteers was incubated with serial logarithmic dilutions of anti-FcepsilonRI and subsequently with antibodies to CD203c PE and CD63 FITC. Sets of samples set up in parallel were lysed with either Saponin based Whole Blood Lysing reagent or with formic acid based Immunoprep/Q-prep. Samples were acquired on a FACS Calibur, but were compensated and analysed offline. Responders were defined as persons who had 10% or more activated basophils above background, or a T(chi) > 4, for two consecutive dilutions of anti-FcepsilonRI antibody. RESULTS: More basophils (median 1164 vs. median 397) and better discrimination of upregulated CD203c and CD63 amongst responders were obtained after lysis with Saponin than after lysis with formic acid. We suggest that CD203c may be a more sensitive marker for the BAT than CD63, as 6/11 responders were found with CD203c, compared with 3/11 with CD63. Most responders (7/11) were identified with probability binning. CONCLUSION: A combination of lysis with Saponin and the markers CD203c and CD63 computed by probability binning may be the most sensitive method of detecting activation of basophils after stimulation through FcepsilonRI.

Journal Article↗
PubMed2005

Body care experienced by people hospitalized with severe respiratory disease.

AIM: The paper gives a theoretical account of experiences of assisted personal body care (APBC) in hospitalized patients with severe chronic obstructive pulmonary disease (COPD). BACKGROUND: Body care has been identified as a central but underestimated area of nursing. Hospitalized patients with severe COPD suffer from breathlessness on exertion and are dependent on help with personal body care. Studies have described patient strategies for managing breathlessness and preferences regarding nursing care during hospitalization. Yet the problems that patients can experience because of their inability to manage personal body care by themselves have not previously been explored. This study explored patients' experiences of being assisted with personal body care. METHODS: A grounded theory methodology was used with a convenience sample of 12 patients. Data were gathered from participant observation of sessions of APBC, in-depth interviews after the observed sessions and measurement of breathlessness perceived by patients before and after the sessions. FINDINGS: The patients perceived body care as a significant daily activity that needed to be carried out in order to preserve their integrity. Dependency and breathlessness, however, impeded the performance of body care activities and patients were struggling for self-preservation. They managed APBC by using a threefold strategy of not letting go, coping with dependency, and minimizing the risk of escalating breathlessness. Two dilemmas were identified as being inherent to the strategy. CONCLUSION: Increased knowledge of the complexities involved in providing assistance might improve nurses' ability to facilitate patients in managing APBC. Dependency is a central issue to address in order to support patients' efforts to preserve integrity and resolve dilemmas inherent to the strategy they use.

Adaptation, Psychological↗
PubMed2004

Exposure to work-related levels of swine dust up-regulates CD106 on human alveolar macrophages.

BACKGROUND: Exposure to dust from swine confinement buildings, causes an inflammatory response. Monocyte recruitment to the murine lung after instillation of lipopolysaccharide (LPS) has been shown to partially depend on CD106/VCAM1. We wanted to determine whether this can be confirmed in man. METHODS: Non-naïve persons bearing personal air samples were exposed for 3 hr in a swine confinement building, and were bronchoscopied before and after exposure. Blood samples were taken at the time of bronchoscopy. Expression of adhesion molecules on leukocytes was investigated by flow cytometry in bronchoaveloar lavage (BAL) and blood. RESULTS: Expression of CD106 on alveolar macrophages, but not on neutrophils or T cells in BAL or blood, was up-regulated in proportion to the amount of LPS that individuals were exposed. CONCLUSIONS: This argues for requirement of CD106 during inflammatory recruitment of monocytes to the human lung.

Air Pollutants, Occupational↗
PubMed2004

Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003.

The nomenclature proposed in the October 2003 report of the Nomenclature Review Committee of the World Allergy Organization is an update of the European Academy of Allergology and Clinical Immunology Revised Nomenclature for Allergy Position Statement published in 2001. The nomenclature can be used independently of target organ or patient age group and is based on the mechanisms that initiate and mediate allergic reactions. It is assumed that as knowledge about basic causes and mechanisms improves, the nomenclature will need further review.

Advisory Committees↗
PubMed2004

Atopic dermatitis -- a total genome-scan for susceptibility genes.

Atopic dermatitis is one of the most common chronic diseases of childhood and closely related to other clinical manifestations of allergy. The incidence is high and still increasing. The genetic contribution to disease development is substantial and complex. Only recently genetic research has begun to focus on this phenotype, and specific susceptibility genes remain to be found. To identify candidate regions holding genes for atopic dermatitis we performed a genome-scan in Danish affected sib-pair families containing sib-pairs matching a phenotype definition of both clinical atopic dermatitis and confirmed specific allergy. The scan was undertaken using 446 microsatellite markers and non-parametric linkage results were obtained from the MAPMAKER/SIBS computer program. We found evidence of linkage to three candidate regions in chromosomes 3p (MLS=2.14), 4p (MLS=2.00) and 18q (MLS=2.25), one of which has not been reported previously. Eight additional regions showed weaker but positive results.

Adult↗
PubMed2004

Inhaled combination therapy with long-acting beta 2-agonists and corticosteroids in stable COPD.

Long-acting beta(2)-agonists (LABAs) have been shown to be effective first-line bronchodilators in the treatment of COPD patients, and inhaled corticosteroids (ICSs) have been shown to reduce the frequency and/or severity of exacerbations in COPD patients. The concomitant use of a LABA and an ICS can influence both airway obstruction (ie, smooth muscle contraction, increased cholinergic tone, and loss of elastic recoil), and airway inflammation (ie, increased numbers of neutrophils, macrophages, and CD8+ lymphocytes, elevated interleukin-8 and tumor necrosis factor-alpha levels, and protease/antiprotease imbalance). They are also able to reduce the total number of bacteria adhering to the respiratory mucosa in a concentration-dependent manner without altering the bacterial tropism for mucosa, and to preserve ciliated cells. Several clinical trials support the concept of inhaled combination therapy with LABAs and corticosteroids in stable COPD patients. This type of therapy not only improves airflow obstruction but also provides clinical benefits, as manifested by sustained reduction in overall symptoms, improvements in health-related quality of life, and reductions in exacerbations. All of these effects are very important because, despite recent advances in our understanding of COPD and its treatment, therapy remains suboptimal for a considerable number of patients.

Administration, Inhalation↗