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Biomedical subjects

A P Perruchoud

Publications and source records attributed to A P Perruchoud.

At least 37 records · Page 2Linked to original sources
PubMed2001

Increased frequency of Chlamydia pneumoniae antibodies in patients with asthma.

The worldwide increase in asthma incidences and the impact of the disease on public health care have led to new investigations of the cause of the disease. Besides well-defined environmental causes, accumulating evidence suggests that respiratory tract infections play an important role in the pathogenesis of asthma. Among these microorganisms Chlamydia pneumoniae is an intracellular pathogen causing persistent infection. Chlamydia pneumoniae infection has been discussed as possibly inducing the development of asthma. This study was designed to investigate the presence of C. pneumoniae-specific IgG, IgA, and IgM antibodies in serum samples of 33 adults with a clinical history of asthma, positive methacholine test, and reduced FEV(1). Patients with asthma were compared with age-, sex-, and locality-matched control subjects (n = 33). We observed no acute infection either in patients with asthma or in control subjects, but 63% of all investigated individuals had signs of past infection. Chlamydia pneumoniae-specific IgA was detected in 52% of the patients with asthma and in 15% of the healthy control subjects (p < 0.01). Serological evidence of chronic infection with C. pneumoniae (high IgG [> pr = 1:512] and high IgA [> or = 1:40]) was more frequent in patients with asthma (18.2%) compared with control subjects (3.0%) (p < 0.01). Our results provide further evidence that chronic infection with C. pneumoniae is linked to asthma.

Adult↗
PubMed2001

Clinical diagnosis of current asthma: predictive value of respiratory symptoms in the SAPALDIA study. Swiss Study on Air Pollution and Lung Diseases in Adults.

Bronchial asthma is a very common disease which often remains underdiagnosed. The aim of this study was to determine the predictive value of the most common respiratory symptoms and to explore the best symptom combinations to predict diagnosis of asthma. A questionnaire comprising common respiratory symptoms was submitted to 9,651 subjects aged 18-60 yrs, randomly selected from the Swiss population, of whom 225 subjects (2.3%) had current asthma as confirmed by their general practitioner. Based on these data the authors calculated the predictive values of single symptoms and symptom combinations to diagnose asthma. Wheezing was the most sensitive single symptom (sensitivity 75%). Simple symptoms such as wheezing with dyspnoea, chronic phlegm or chronic cough had specificity greater than 95%. Wheezing with dyspnoea (WD) or nocturnal dyspnoea (ND) had the best positive predictive value (PPV) as isolated symptoms (24% and 21%, respectively). When combining symptoms, wheezing associated with daily dyspnoea at rest or nocturnal dyspnoea showed the best PPV (42% and 39%, respectively), almost double single symptoms such as WD or ND. Wheezing associated with at least two of the three nocturnal symptoms (nocturnal dyspnoea, nocturnal cough or nocturnal chest tightness) had a sensitivity of 80% to diagnose asthma. In conclusion, respiratory symptoms obtained by medical history are reliable predictors of asthma. The findings suggest that particular combinations of symptoms are clinically useful in the differential diagnosis of asthma.

Adolescent↗
PubMed2000

[Early detection of exacerbation of lung infections in patients with cystic fibrosis by means of daily spirometry].

UNLABELLED: The clinical course of cystic fibrosis is characterised by pulmonary involvement with mucus retention, chronic pulmonary infection and parenchymal inflammation. Recurrent infectious exacerbations are usually accompanied by a fall in lung volumes. This pilot study investigated whether exacerbations can be detected early by daily spirometry. Ten patients with cystic fibrosis (5 female; 5 male; mean age 24.9 years) performed daily spirometry using a portable transtelephonic spirometer (Spirophone). Infectious exacerbations were diagnosed on clinical grounds and treated without knowledge of the spirometry results. Data of 9 patients recorded over a period of 5-11 months were analysed. One patient was excluded due to non-compliance. A total of 20 infectious exacerbations occurred during the observation period. A fall of at least 20% in one or more of the following parameters was observed in 90% (18/20) of exacerbations: FVC, FEV1, PEF, and FEF25/75. A daily drop in lung volumes of 0.7% to 1.2% was recorded beginning at a median of 33 (20 to 120) days before infectious exacerbations were diagnosed. There was a 2-3% daily improvement in spirometric data under treatment with antibiotics. CONCLUSION: Daily spirometry allows early recognition of pulmonary infectious exacerbations in patients with cystic fibrosis. Daily spirometry may be used as an indicator for early antibiotic treatment.

Adolescent↗
PubMed2000

Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety.

OBJECTIVES: To determine whether use of an oral nicotine inhaler can result in long term reduction in smoking and whether concomitant use of nicotine replacement and smoking is safe. DESIGN: Double blind, randomised, placebo controlled trial. Four month trial with a two year follow up. SETTING: Two university hospital pulmonary clinics in Switzerland. PARTICIPANTS: 400 healthy volunteers, recruited through newspaper advertisements, willing to reduce their smoking but unable or unwilling to stop smoking immediately. INTERVENTION: Active or placebo inhaler as needed for up to 18 months, with participants encouraged to limit their smoking as much as possible. MAIN OUTCOME MEASURES: Number of cigarettes smoked per day from week six to end point. Decrease verified by a measurement of exhaled carbon monoxide at each time point compared with measurement at baseline. RESULTS: At four months sustained reduction of smoking was achieved in 52 (26%) participants in the active group and 18 (9%) in the placebo group (P<0.001; Fisher's test). Corresponding figures after two years were 19 (9.5%) and 6 (3.0%) (P=0.012). CONCLUSION: Nicotine inhalers effectively and safely achieved sustained reduction in smoking over 24 months. Reduction with or without nicotine substitution may be a feasible first step towards smoking cessation in people not able or not willing to stop abruptly.

Administration, Inhalation↗
PubMed2000

[SAPALDIA: past, present and future].

The cross-sectional part of SAPALDIA studied the associations between respiratory symptoms or functional abnormalities and chronic exposure to a polluted environment. The results showed an elevated risk of developing respiratory symptoms in regions with higher levels of particulate matters (PM10). The same was observed with passive smoking exposure. Decreased spirometric parameters (especially FVC) were measured in areas with the highest levels of PM10. While the functional alteration is clinically minimal in the individual, the effect is significant when one considers the prevalence of an abnormal functional parameter in a general population. Exposure to pollutants at the workplace increases bronchial reactivity to non-specific stimuli, with atopy acting as amplifier of this effect. The longitudinal part of SAPALDIA examined the associations between the dynamics of respiratory symptoms or functional abnormalities and average levels, as well as short-term fluctuations, of atmospheric pollutants. It was observed that symptomatic episodes tend to last longer in more polluted regions, whichever marker of pollution is used (PM10 or NO2). Passive smoking tends to prolong respiratory symptoms and shorten asymptomatic intervals. Short-term increases in outdoor pollutants are associated with an increase in incidence of peak flows below individual baseline values. Numerous questions remain regarding the relationship between respiratory health and environment. A SAPALDIA II study is under preparation which will follow the evolution of SAPALDIA I participants with regard to respiratory symptoms, pulmonary function, bronchial reactivity and markers of atopy.

Air Pollution↗
PubMed2000

P21 gene expression as an indicator for the activity of adenovirus-p53 gene therapy in non-small cell lung cancer patients.

Alterations in the tumor suppressor gene p53 lead to impaired cell cycle control, allowing for the development and growth of tumors. To restore a loss of p53 function, we performed a phase I study of intratumoral gene therapy with adenovirus expressing wild-type p53 in patients with non-small cell lung cancer carrying mutations in the p53 gene. Furthermore, in a phase II study, gene therapy was complemented with simultaneous cisplatin/vinorelbine treatment. Biopsies were obtained from all treated patients before and 24-48 hours after gene therapy to study changes in the expression of p53 target genes. We report here that in most of the cases, the target gene p21 was up-regulated, especially when injection of higher doses of p53-expressing adenovirus was combined with simultaneous chemotherapy, whereas Pig3, previously reported to be highly up-regulated by p53, generally did not show a clear increase. Interestingly, a clear p21 gene response was observed only in tumors showing stabilization or regression. We conclude that p21 appears to be up-regulated after adenovirus-mediated p53 gene transfer and is the most sensitive marker tested for biological response to gene therapy in the small cohort of non-small cell lung cancers that were studied.

Adenoviridae↗
PubMed2000

Exposure to motor vehicle traffic and allergic sensitization. The Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) Team.

We examined the association between the presence of an allergic sensitization and seasonal allergic diseases or symptoms and the exposure to road traffic in Basel, Switzerland. Traffic counts at the domiciles of subjects ranged from 24 to 32,504 cars per 24 hours, with a median of 1,624. To investigate the relation of road traffic and allergies, we matched the data of the traffic inventory of Basel with those of the 820 participants of the SAPALDIA study (Swiss Study on Air Pollution and Lung Diseases in Adults), ages 18-60 years, who had completed a detailed respiratory health questionnaire and had undergone allergy testing (skin prick tests and serologic examinations). We observed a positive association with a sensitization to pollen that was most pronounced among persons with a duration of residence of at least 10 years. The odds ratios (adjusted for educational level, smoking behavior, number of siblings, age, sex, and family history of atopy) for cars, contrasting four exposure categories with the lowest quartile as referent category, were 1.99 [95% confidence interval (CI) = 0.91-4.38], 2.47 (95% CI = 1.06-5.73), and 2.83 (95% CI = 1.26-6.31). These results suggest that living on busy roads is associated with a higher risk for a sensitization to pollen and could possibly be interpreted as an indication for interactions between pollen and air pollutants. We did not, however, find a similar relation between motor vehicle traffic and hay fever or seasonal allergic symptoms, and we saw no trend that increasing traffic exposure was associated with a rise in sensitization rates to indoor allergens.

Adult↗
PubMed2000

Hypoxia modifies the effect of PDGF on glycosaminoglycan synthesis by primary human lung cells.

Hypoxia, a consequence of interstitial lung diseases, may lead to secondary pulmonary hypertension and pulmonary vascular remodeling. Hypoxia induces activation and proliferation of lung cells and enhances the deposition of extracellular matrix including glycosaminoglycans (GAGs). To elucidate the cell biological mechanisms underlying the development of secondary pulmonary hypertension, we studied the effect of hypoxia on GAG synthesis by human lung cells. GAG synthesis was measured by incorporation of [(3)H]glucosamine; GAGs were isolated, purified, and characterized with GAG-degrading enzymes. Fibroblasts and vascular smooth muscle cells (VSMCs) synthesized hyaluronic acid, heparan sulfate, and chondroitin sulfates, whereas dermatan sulfate was found only in fibroblasts. Hypoxia did not influence the size or charge of the individual GAGs. However, hypoxia inhibited platelet-derived growth factor-induced [(3)H]glucosamine incorporation in secreted GAGs, especially hyaluronic acid, in VSMCs. In contrast, it stimulated GAG secretion, specifically heparan sulfate, by fibroblasts. Our results indicate that hypoxia induces modifications in GAG synthesis by human lung VSMCs and fibroblasts that may be correlated to pathophysiological manifestations in lung diseases causing hypoxia.

Cell Hypoxia↗
PubMed2000

Takayasu disease with predominant pulmonary involvement.

We report a case of Takayasu's arteritis with predominant pulmonary involvement, which led eventually to complete obliteration of the right pulmonary artery. Subsequently, cavitation and chronic inflammation developed in the nonperfused right lung. A right pneumonectomy was performed to control the infectious process, leading to functional improvement and better control of the underlying immunologic disorder.

Adult↗
PubMed2000

Prospective randomized comparison of thoracoscopic talc poudrage under local anesthesia versus bleomycin instillation for pleurodesis in malignant pleural effusions.

Induction of pleurodesis offers benefit for patients with metastatic tumors and symptomatic malignant pleural effusions, but the best method for achieving this is still unknown. In this prospective, randomized comparison of two well-established pleurodesis procedures, 36 patients with malignant pleural effusions, expanded lungs after drainage, and expected survival of > 1 mo received either bleomycin instillation (60E) via a small-bore thoracostomy tube or thoracoscopic talc poudrage (5 g) under local anesthesia. Efficacy, safety, and cost could be evaluated for 32 treatments (17 bleomycin, 15 talc) in 31 patients. Recurrence rates of effusion with bleomycin and talc poudrage after 30 d were 41% and 13% (p = 0.12), respectively, those after 90 d were 59% and 13%, respectively (p = 0.01), and those after 180 d were 65% and 13% (p = 0.005), respectively. Neither procedure showed any major adverse effect, and both were equally well tolerated. Cost estimation favored thoracoscopic talc poudrage, both for the initial hospitalization and with regard to recurrences. In conclusion, thoracoscopic talc pleurodesis under local anesthesia is superior to bleomycin instillation for pleurodesis in cases of malignant pleural effusion.

Aged↗
PubMed2000

Occupational exposure to inhalative irritants and methacholine responsiveness.

OBJECTIVES: Occupational exposures to inhalative irritants have been associated with an increased reporting of respiratory symptoms in previous studies. Methacholine responsiveness represents a continuous measure of airway responsiveness. As such, it may be less subject to recall bias and more sensitive to detecting effects of occupational exposure on airways. Such effects may be stronger among atopic persons. The objective of the study was to examine the relationship between self-reports of occupational exposure to dusts, gases, vapors, aerosols, and fumes and methacholine responsiveness. METHODS: A sample was studied of never smokers (N=3044) chosen randomly from 8 areas in Switzerland. Atopy was defined as any positive skin test to 8 inhalative allergens. Nonspecific bronchial reactivity was tested using methacholine chloride and quantified by calculating the slope of the dose-response. RESULTS: The methacholine slopes were 19% [95% confidence interval (95% CI) 6-32] higher for never smokers with exposure to dusts, fumes, vapors, gases, or aerosols than for the unexposed group. When only atopic never smokers were examined. the increase was larger (37%, 95% CI 7-75), and for persons with >2 positive skin prick tests the effect was still higher (42%, 95% CI -1.5-104). Exposure to vapors and aerosols was strongly associated with increased methacholine slopes among the atopic subjects. CONCLUSIONS: Occupational exposure, particularly to dusts and fumes, was associated with increased bronchial reactivity in never smokers in this study. The magnitude of the effect was larger among atopic subjects.

Adolescent↗
PubMed2000

Clinical efficacy and safety of fluticasone propionate 1 mg per day administered via a HFA 134a pressurized metered dose inhaler to patients with moderate to severe asthma. International study group.

This multi-national, double-blind, randomized, parallel-group study compared the efficacy and tolerability of fluticasone propionate 500 microg twice daily propelled either by the non-chlorofluorocarbon (CFC) propellant, hydrofluoroalkane (HFA) 134a, or the CFC propellants 11 and 12 used in the established pressurized metered dose inhaler (pMDI). The study period was 12 months and involved 412 subjects with moderate to severe asthma (HFA 134a pMDI: n = 203; CFC pMDI: n = 209). For the first 3 months, subjects kept a daily record card and attended the clinic every 4 weeks. Thereafter, they kept daily diaries for 2 weeks before each clinic assessment, which were performed at the end of 6, 9 and 12 months. Mean morning peak expiratory flow (PEF) increased during the first week in both treatment groups. By the end of week 12 the adjusted mean increase from baseline in morning PEF was 21 and 23 l min(-1) in the HFA 134a and CFC pMDI groups, respectively, and this increase was maintained throughout the 12-month study period. Similar improvements were detected in other diary card parameters and in clinic lung function measurements. The two groups were shown to be clinically equivalent in terms of all efficacy variables and there were no differences in tolerability. There were few reports of low serum cortisol levels during the 12-month study period, and serum cortisol levels were similar at baseline and after 12 weeks and 12 months of treatment in the two groups. In conclusion, the new HFA 134a fluticasone propionate pMDI is as effective and safe as the established CFC fluticasone propionate pMDI when used at a dosage of 1 mg day(-1).

Administration, Inhalation↗
PubMed1999

Calcium channel blockers activate the interleukin-6 gene via the transcription factors NF-IL6 and NF-kappaB in primary human vascular smooth muscle cells.

BACKGROUND: Calcium channel blockers (CCB) of all subclasses: the dihydropyridines, benzothiazepines, and phenylalkylamines, at nanomolar concentrations, have been shown to up-regulate interleukin-6 (IL-6) mRNA. We investigated the underlying molecular mechanism responsible for IL-6 induction in response to the CCB amlodipine, diltiazem, and verapamil in primary human vascular smooth muscle cells (VSMC). METHODS AND RESULTS: All 3 CCB directly activated transcription of the human IL-6 gene in primary human VSMC in a time- and dose-dependent manner, as demonstrated by luciferase reporter gene assays using a 651-bp fragment of the human IL-6 gene promoter. Deletion analysis of the IL-6 promoter revealed that CCB inducible promoter activity was localized to a 160-bp fragment directly upstream of the transcriptional start site of the IL-6 gene. Known transcription factor consensus sequences within this fragment include a NF-IL6 and a NF-kappaB site. Site-directed mutagenesis suggested that both transcription factors had positive regulatory activity and cooperatively transmitted induction of the IL-6 gene by CCB. The data are confirmed by electrophoretic mobility shift analyses using nuclear extracts from CCB-stimulated and control primary VSMC. CCB of all subclasses increased DNA binding of NF-IL6 and NF-kappaB as early as 30 minutes after stimulation with the drugs. This effect was independent of intracellular calcium concentrations because calcium-free medium did not increase NF-IL6 or NF-kappaB activity. CONCLUSIONS: The results demonstrate that CCB of all 3 subclasses are capable of activating NF-IL6 and NF-kappaB. CCB may thus directly regulate cellular functions by affecting the activity of transcription factors independent of changes of intracellular calcium concentrations, an observation that is of interest considering the biological effects induced by CCB.

CCAAT-Enhancer-Binding Proteins↗
PubMed1999

Transforming growth factor-beta1 induces interleukin-6 expression via activating protein-1 consisting of JunD homodimers in primary human lung fibroblasts.

Transforming growth factor (TGF)-beta1 induces extracellular matrix deposition and proliferation of mesenchymal cells. We recently reported that interleukin (IL)-6 is an essential mediator of growth factor-induced proliferation of lung fibroblasts. Here, we demonstrate by reverse transcriptase polymerase chain reaction and enzyme-linked immunoassay that TGF-beta1 is a potent inducer of IL-6 mRNA and protein in primary human lung fibroblasts. Transient transfections of fibroblasts with a luciferase reporter gene construct containing nucleotides -651 to +1 of the human IL-6 promoter revealed that TGF-beta1 also potently activated IL-6 promoter activity. Progressive 5'-deletions and site-directed mutagenesis of the parental construct located the TGF-beta1-responsive cis-regulatory element to a known activating protein-1 (AP-1) sequence (nucleotides -284 to -276). Gel shift analyses revealed that AP-1 DNA binding activity in nuclear extracts was increased 30 min after stimulation with TGF-beta1. In contrast, neither CCAAT enhancer-binding protein-beta, NF-kappaB, nor Sp1 were activated by TGF-beta1. Supershift analyses demonstrated that the AP-1 complex induced by TGF-beta1 was composed of Jun isoforms and absent of Fos isoforms. Moreover, this complex was found to be a JunD homodimer. Our data thus demonstrate that TGF-beta1 is a potent inducer of IL-6 in primary human lung fibroblasts. The TGF-beta1-activated JunD homodimer may be essential for a majority of the biological effects induced by TGF-beta1 in this cell type, such as proliferation and extracellular matrix synthesis.

Base Sequence↗
PubMed1999

[Is self-management practical in bronchial asthma?].

The threat and uncertainty involved in an asthma attack reduce the quality of life for the patient. Life quality can be improved if the patient learns self-management principles. This is easy to learn and involves a simple procedure requiring the patient to refer to written instructions in the event of an asthma exacerbation. As a basis for treatment the patient needs to measure maximum peak flow, which can be done with an easy-to-use peak flow meter. A value above 80% of the personal best indicates that the treatment has been successful. By means of printed instructions in credit card format, the appropriate treatment for particular peak flow values and/or symptoms can be looked up and administered. So far there have been no self-management studies providing a definite answer on what interventions are effective and cost-effective. One clear result is that inhaled steroid therapy must be initiated early. Learning self-management patently leads to improvement in the patient's life quality and safety. In the long run this concept appears to be cost-saving with regard to days lost through sickness and hospitalization.

Anti-Asthmatic Agents↗