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Biomedical subjects

Thierry Rochat

Publications and source records attributed to Thierry Rochat.

At least 19 recordsLinked to original sources
PubMed2006

Chronic rhinoviral infection in lung transplant recipients.

RATIONALE: Lung transplant recipients are particularly at risk of complications from rhinovirus, the most frequent respiratory virus circulating in the community. OBJECTIVES: To determine whether lung transplant recipients can be chronically infected by rhinovirus and the potential clinical impact. METHODS: We first identified an index case, in which rhinovirus was isolated repeatedly, and conducted detailed molecular analysis to determine whether this was related to a unique strain or to re-infection episodes. Transbronchial biopsies were used to assess the presence of rhinovirus in the lung parenchyma. The incidence of chronic rhinoviral infections and potential clinical impact was assessed prospectively in a cohort of 68 lung transplant recipients during 19 mo by screening of bronchoalveolar lavages. MEASUREMENTS AND MAIN RESULTS: We describe 3 lung transplant recipients with graft dysfunctions in whom rhinovirus was identified by reverse transcriptase-polymerase chain reaction in upper and lower respiratory specimens over a 12-mo period. In two cases, rhinovirus was repeatedly isolated in culture. The persistence of a unique strain in each case was confirmed by sequence analysis of the 5'NCR and VP1 gene. In the index case, rhinovirus was detected in the lower respiratory parenchyma. In the cohort of lung transplant recipients, rhinoviral infections were documented in bronchoalveolar lavage specimens of 10 recipients, and 2 presented with a persistent infection. CONCLUSIONS: Rhinoviral infection can be persistent in lung transplant recipients with graft dysfunction, and the virus can be detected in the lung parenchyma. Given the potential clinical impact, chronic rhinoviral infection needs to be considered in lung transplant recipients.

Adolescent↗
PubMed2006

A prospective hospital-based study of the clinical impact of non-severe acute respiratory syndrome (Non-SARS)-related human coronavirus infection.

BACKGROUND: In addition to the human coronaviruses (HCoVs) OC43 and 229E, which have been known for decades to cause infection in humans, 2 new members of this genus have recently been identified: HCoVs NL63 and HKU1. Their impact as a cause of respiratory tract disease in adults at risk for complications needs to be established. METHODS: We prospectively assessed the clinical impact of coronavirus infection (excluding cases of severe acute respiratory syndrome) among hospitalized adults. All patients with respiratory disease for whom bronchoalveolar lavage was performed were screened by reverse-transcriptase polymerase chain reaction for the presence of all 4 HCoVs. RESULTS: HCoV was identified in 29 (5.4%) of 540 bronchoalveolar lavage fluid specimens from 279 subjects (mean age, 51 years; 63% male). HCoV OC43 was identified most frequently (12 isolates), followed by 229E (7 isolates), NL63 (6 isolates), and HKU1 (4 isolates). In all, 372 (69%) of 540 bronchoalveolar lavage fluid specimens were negative for bacteria, and 2 persons were coinfected with other respiratory viruses. Transplantation was the most common underlying condition. Of the 29 patients who had HCoV identified in their bronchoalveolar lavage fluid specimens, 9 (31%) were hospitalized in the intensive care unit, 22 (76%) presented to the hospital with acute respiratory symptoms, 16 (55%) presented with cough and/or sputum, 13 (45%) presented with dyspnea, 16 (55%) had experienced prior respiratory infection, and 18 (62%) had a new infiltrate that was visible on chest radiograph. The most frequent final diagnosis was a lower respiratory tract infection. CONCLUSIONS: The recently discovered HCoVs NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infection. Our study also suggests that coronaviruses contribute to respiratory symptoms in most cases.

Adolescent↗
PubMed2006

Respiratory effects of environmental tobacco exposure are enhanced by bronchial hyperreactivity.

RATIONALE: Exposure to environmental tobacco smoke (ETS) is associated with increased reports of respiratory symptoms and reduced lung function, but the long-term effects of ETS are unclear, notably in healthy individuals with bronchial hyperresponsiveness (BHR). OBJECTIVE: To assess the longitudinal effects of ETS exposure on the development of respiratory symptoms and spirometry in subjects with BHR. METHODS: The study population included 1,661 never-smokers from the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cohort, assessed in 1991 (baseline) and 11 yr later, who were symptom-free at baseline. Incident reports of respiratory symptoms and results of spirometry were assessed at the follow-up survey. MAIN RESULTS: Exposure to ETS reported in the two surveys was strongly associated with the development of cough (odds ratio, 2.1; 95% confidence interval, 1.2-3.7; p = 0.01). In subjects with BHR exposed to ETS at both surveys, a trend for strong associations were observed for wheeze, cough, dyspnea, and chronic bronchitis; however, the association reached statistical significance only for the symptom of dyspnea (p < 0.01). Lower FEV1/FVC (mean +/- SD, 72.9 +/- 7.7 vs. 76.8 +/- 6.1%; p < 0.01) and FEF(25-75) (forced expiratory flow, midexpiratory phase)/FVC (mean +/- SD, 56.1 +/- 22.5 vs. 68.1 +/- 21.6%; p < 0.01) were observed in subjects with BHR exposed to ETS compared with nonexposed subjects without BHR. Lower values were found in subjects continuing exposure by the follow-up survey. CONCLUSION: Exposure to ETS was strongly associated with the development of respiratory symptoms in previously asymptomatic subjects with BHR within 11 yr. Furthermore, subjects with underlying BHR had reduced lung function at follow-up, thus suggesting a higher risk for the development of chronic respiratory disease in this subset of the population.

Adult↗
PubMed2006

Ascites and highly elevated CA-125 levels in a case of peritoneal tuberculosis.

Peritoneal tuberculosis (PT) is uncommon in industrialized countries. We report the case of a 35-y-old female with a 1-y history of abdominal discomfort, ascites, systemic symptoms, and highly elevated CA-125 suggesting malignancy, in whom the diagnosis of PT was considered. Both clinical symptoms and CA-125 levels regressed under tuberculostatic treatment.

Adult↗
PubMed2005

[Is intrinsic or non-atopic asthma a particular disease?].

Intrinsic or non-atopic asthma is defined by the absence of positive skin test for specific aero-allergens, together with the absence of specific serum IgE. In the adult population, about one third of asthmatic patients are non-atopic. Non-atopic asthma begins generally later in life and is often more severe than atopic asthma. It is more often associated with chronic sinusitis and nasal polyps, a fact that is often underestimated. At the cellular and molecular level, non-atopic asthma and atopic asthma a very similar, and the reason for their clinical difference is not really understood.

Asthma↗
PubMed2005

A new educational program for patients suffering from sleep apnea syndrome.

OBJECTIVE: Patients' knowledge and beliefs about their chronic illnesses such as OSAS are known to influence a range of health related variables, including treatment compliance. It is for that reason that this interdisciplinary program centred on the therapeutic education of the patients was conceived by two medical teams with the aim of creating a new coverage of the patients affected of OSAS. METHODS: Thirty-five OSAS patients were consecutively collected among those regularly followed at the Service of pneumology outpatient facility. The psycho-educational methodology as well as the courses are described in detail. Patients were admitted for 36 h at the Service of Therapeutic Education for Chronic Diseases for both individual and group multidisciplinary approach to their disease. Groups of 3-4 patients discuss benefits, inconvenience as well as CPAP representations and manipulation of the device in small workshops. RESULTS: The therapeutic objectives, the educational methods, the program evaluation are presented. Preliminary results show a clinical improvement of the duration of CPAP use (0.7 +/- 0.2 h/night). 24% of patients increased the CPAP use more than one hour per night 3 months later. The Epworth sleepiness scale is significantly improved 3 months later (p < 0.05). CONCLUSION: We describe a new therapeutic educational interdisciplinary program for patients affected by OSAS. Its efficacy will be tested prospectively in a larger group and in the long term. PRACTICE IMPLICATIONS: The educational methods were applicable to the patients affected of OSAS bringing new specific strategies to improve the CPAP use. Patients had a positive attitude towards the CPAP treatment.

Continuous Positive Airway Pressure↗
PubMed2005

Long-term cultures of polarized airway epithelial cells from patients with cystic fibrosis.

The poor ability of respiratory epithelial cells to proliferate and differentiate in vitro into a pseudostratified mucociliated epithelium limits the general use of primary airway epithelial cell (AEC) cultures generated from patients with rare diseases, such as cystic fibrosis (CF). Here, we describe a procedure to amplify AEC isolated from nasal polyps and generate long-term cultures of the respiratory epithelium. AEC were seeded onto microporous permeable supports that carried on their undersurface a preformed feeder layer of primary human airway fibroblasts. The use of fibroblast feeder layers strongly stimulated the proliferation of epithelial cells, allowing the expansion of the cell pool with successive passages. AEC at increasing passage were seeded onto supports undercoated with airway fibroblasts and exposed to air. Either freshly isolated or amplified AEC could differentiate into a pseudostratified mucociliated epithelium for at least 10 mo. Thus, CF epithelia cultures showed elevated Na+ transport, drastic hyperabsorption of surface liquid, and absence of cAMP-induced Cl- secretion as compared with non-CF cultures. They were also characterized by thick apical secretion that hampered the movement of cell surface debris by cilia. However, CF respiratory epithelia did not show increased production of mucins or IL-8. The method described here is now routinely used in our laboratory to establish long-term cultures of well differentiated respiratory epithelia from human airway biopsies.

Biological Transport↗
PubMed2005

Body composition in patients with chronic hypercapnic respiratory failure.

STUDY OBJECTIVE: To evaluate the contribution of body composition measurements to clinical assessment in patients on home nasal positive-pressure ventilation for chronic hypercapnic respiratory failure (CHRF), and their relationship to respiratory impairment. METHODS: Patients with CHRF (restrictive lung disease (RLD), n=37; chronic obstructive pulmonary disease (COPD), n=19), during elective yearly evaluations underwent pulmonary function testing (forced expiratory volumes, arterial blood gases, maximal inspiratory and expiratory pressure (PI(max) or PE(max))), and bioelectrical impedance analysis to determine fat-free mass (FFM) index (kg/m(2)) and body fat mass index. RESULTS: When compared with age- and sex-matched healthy controls, RLD patients (OR 5.5, CI 1.9-15.6, P<0.002) and COPD (OR 5.2, CI 1.1-24.9, P=0.04) were significantly more likely to have a low FFM index. Roughly one-half of patients with RLD and one-third with COPD had abnormally low FFM index. Estimation of nutritional status by body mass index (BMI) alone clearly underestimated the prevalence of FFM index depletion. Muscle mass assessed by FFM index explained 26% of variance of PI(max) (P<0.001) and 27% of that of PE(max) (P<0.001). CONCLUSION: BMI alone clearly underestimated FFM depletion, and presence of a very high body fat mass index. Indeed, normal or high BMI can be associated with FFM depletion. Because of its relationship to respiratory muscle strength, an assessment of FFM appears to be valuable in CHRF.

Adolescent↗
PubMed2005

Effects of amphotericin B on ion transport proteins in airway epithelial cells.

Topical intranasal application of the antifungal Amphotericin B (AmphoB) has been shown as an effective medical treatment of chronic rhinosinusitis. Because this antibiotic forms channels in lipid membranes, we considered the possibility that it affects the properties and/or cell surface expression of ion channels/pumps, and consequently transepithelial ion transport. Human nasal epithelial cells were exposed apically to AmphoB (50 microM) for 4 h, 5 days (4 h daily), and 4 weeks (4 h daily, 5 days weekly) and allowed to recover for 18-48 h. AmphoB significantly reduced transepithelial potential difference, short-circuit current, and the amiloride-sensitive current. This was not due to generalized cellular toxicity as judged from normal transepithelial resistance and mitochondrial activity, but was related to inhibitory effects of AmphoB on ion transport proteins. Thus, cells exposed to AmphoB for 4 h showed decreased apical epithelial sodium channels (ENaC) activity with no change in basolateral Na(+)K(+)-ATPase activity and K(+) conductance, and reduced amount of alphaENaC, alpha1-Na(+)K(+)-ATPase, and NKCC1 proteins at the cell membrane, but no change in mRNA levels. After a 5-day treatment, there was a significant decrease in Na(+)K(+)-ATPase activity. After a 4-week treatment, a decrease in basolateral K(+) conductance and in alphaENaC and alpha1-Na(+)K(+)-ATPase mRNA levels was also observed. These findings may reflect a feedback mechanism aimed to limit cellular Na(+) overload and K(+) depletion subsequently to formation of AmphoB pores in the cell membrane. Thus, the decreased Na(+) absorption induced by AmphoB resulted from reduced cell surface expression of the ENaC, Na(+)K(+)-ATPase pump and NKCC1 and not from direct inhibition of their activities.

Amphotericin B↗
PubMed2005

Severe left ventricular dysfunction secondary to primary pulmonary hypertension: bridging therapy with bosentan before lung transplantation.

When right ventricular failure develops secondary to primary pulmonary hypertension, right-left ventricular interaction may lead to severe impairment of left ventricular function. In such cases, many experts favor combined heart-lung transplantation by fear that the left ventricle may not recover after transplantation of the lungs alone. We report a case of primary pulmonary hypertension with severely diminished right and left ventricular function. The patient was rendered amenable to isolated pulmonary transplantation with the endothelin-receptor antagonist bosentan. The medication improved right and left ventricular function to the point that heart transplantation no longer appeared necessary. After double-lung transplantation the patient's cardiac function made a full recovery. This approach might be particularly welcome considering both the current donor organ shortage and the limited number of surgical teams with expertise in heart-lung transplantation.

Adult↗
PubMed2005

Health-related quality of life following single or bilateral lung transplantation: a 7-year comparison to functional outcome.

OBJECTIVES: To compare long-term health-related quality of life (HRQL) in single and bilateral lung transplant recipients independent of the underlying disease, and in a subset of patients with native pulmonary emphysema. METHODS: Forty-four lung transplant recipients (mean [+/- SD] age, 44.8 +/- 11.6 years) were followed up for > 2 years after single lung transplantation (LTx) [14 recipients] or bilateral LTx (30 recipients). Data were prospectively collected, before undergoing LTx and annually after undergoing LTx, measuring FEV1, 6-min walk test (6MWT) results, and quality of life using the St. George respiratory questionnaire (SGRQ) and a visual analog scale (VAS). The SGRQ addresses three domains, namely, respiratory symptoms, accomplishment of routine activities, and disease impact on daily life. RESULTS: Statistically significant correlation coefficients were found comparing the SGRQ and the VAS (r = 0.812; p < 0.0001), the SGRQ and the 6MWT (r = 0.610; p < 0.0001), and the SGRQ and the FEV1 (r = 0.523; p < 0.0001) in all patients. Significant improvements on the FEV1, 6MWT, and SGRQ were observed after LTx in both single and bilateral LTx recipients. Increased risk for the development of bronchiolitis obliterans syndrome (BOS) [relative risk, 2.86; 95% confidence interval, 1.22 to 6.67; p = 0.03] and significantly lower FEV1 values were observed in patients following a single graft, compared to that in patients following a bilateral graft (p < 0.01). In contrast, the 6MWT and the SGRQ scores were not significantly different between recipients of single and double LTx. The same patterns of results were observed in comparisons between single and bilateral lung recipients with prior pulmonary emphysema. CONCLUSIONS: Despite poorer FEV1 recovery and increased risk of BOS after LTx, single lung transplant recipients had comparable long-term exercise tolerance and quality-of-life scores as patients who received bilateral transplants. These results suggest the limited influence of functional performance on objective and subjective markers of HRQL recovery after LTx.

Adult↗
PubMed2005

Rapid eye movement-related disordered breathing: clinical and polysomnographic features.

OBJECTIVE: The existence of a rapid eye movement (REM)-specific sleep-disordered breathing (SDB) has been suggested based on the finding of an association between sleepiness and respiratory disturbances confined primarily to REM sleep. The aim of the study was to define the frequency and the clinical and polysomnographic features of REM SDB in a large clinical population. METHODS: Anthropometric, clinical, and polysomnographic characteristics of 415 patients undergoing polysomnography for SDB were examined. For all patients the apnea-hypopnea index (AHI) during total sleep time, the AHI during REM (AHI-REM), and the AHI during non-REM sleep (AHI-NREM) were calculated. REM SDB was defined as an AHI-REM/AHI-NREM ratio >2. Patients were stratified according to the severity of disease in mild, moderate, and severe cases. Daytime sleepiness was assessed subjectively by the Epworth sleepiness scale (ESS), and objectively, in a subgroup of 228 patients, by the maintenance wakefulness test (MWT). RESULTS: Of the initial sample, 36.4% of cases (n = 151) fulfilled the REM SDB criteria. No significant differences in subjective complaints, medical history, and drug intake were present between REM and non-REM SDB patients, and no significant differences were found in ESS scores and mean sleep latency of the MWT between groups. A high occurrence of REM SDB was found in mild (73.1%) and moderate cases (47.2%). While in the entire group and in non-REM SDB patients a strong male prevalence was found, the incidence of REM SDB was similar in men and women. CONCLUSION: Our results show that neither clinical history nor daytime sleepiness differentiate patients with REM SDB from non-REM SDB patients. The disorder is more common in mild and moderate cases; there is an equal incidence in women and men. These findings may suggest that REM-related SDB is a part of the spectrum of SDB.

Adult↗
PubMed2004

Lower respiratory viral illnesses: improved diagnosis by molecular methods and clinical impact.

We assessed the frequency and the potential role of respiratory viruses on disease outcomes in hospitalized patients and lung transplant recipients who underwent a bronchoalveolar lavage (BAL) for an acute respiratory infection. BAL specimens (148) were analyzed by reverse transcription-polymerase chain reaction for the presence of 11 different viruses, as well as Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. Respiratory viruses were identified in 34 of 117 BAL specimens (29%) obtained in patients with a suspected respiratory infection and in only 2 of 31 control subjects (7%) (p < 0.01). M. pneumoniae was identified in five additional cases. Only 30% of cases that were virus positive by molecular methods were also positive by cell culture analysis. Rhinovirus was the most frequently identified virus (56% of cases) followed by respiratory syncytial virus (27%). In lung transplant recipients, the rate of viral infections was 55% in cases with respiratory symptoms compared with only 4% in control subjects (p < 0.001). In these cases, respiratory viral infections were associated with significant lung function abnormalities. By using reverse transcription-polymerase chain reaction assays, we frequently identified respiratory viruses in BAL specimens of patients hospitalized with lower respiratory tract infections. These viruses were associated with high morbidity, particularly in lung transplant recipients.

Bronchoalveolar Lavage Fluid↗
PubMed2004

N-acetylcysteine inhibits Na+ absorption across human nasal epithelial cells.

N-acetylcysteine (NAC) is a widely used mucolytic drug in patients with a variety of respiratory disorders. The mechanism of action is based on rupture of the disulfide bridges of the high molecular glycoproteins present in the mucus, resulting in smaller subunits of the glycoproteins and reduced viscosity of the mucus. Because Na(+) absorption regulates airway surface liquid volume and thus the efficiency of mucociliary clearance, we asked whether NAC affects the bioelectric properties of human nasal epithelial cells. A 24-h basolateral treatment with 10 mM of NAC decreased the transepithelial potential difference and short-circuit current (I(SC)) by 40%, and reduced the amiloride-sensitive current by 50%, without affecting the transepithelial resistance. After permeabilization of the basolateral membranes of cells with amphotericin B in the presence of a mucosal-to-serosal Na(+) gradient (135:25 mM), NAC inhibited 45% of the amiloride-sensitive current. The Na(+)-K(+)-ATPase pump activity and the basolateral K(+) conductance were not affected by NAC treatment. NAC did not alter total cell mRNA and protein levels of alpha-epithelial Na(+) channel (EnaC) subunit, but reduced abundance of alpha-ENaC subunits in the apical cell membrane as quantified by biotinylation. This effect can be ascribed to the sulphydryl (SH) group of NAC, since N-acetylserine and S-carboxymethyl-l-cysteine were ineffective. Given the importance of epithelial Na(+) channels in controlling the thin layer of fluid that covers the surface of the airways, the increase in the fluidity of the airway mucus following NAC treatment in vivo might be in part related to downregulation of Na(+) absorption and consequently water transport.

Acetylcysteine↗
PubMed2004

Electrogastrography reveals post-prandial gastric dysmotility in children with cystic fibrosis.

OBJECTIVES: Cystic fibrosis patients have a wide spectrum of gastrointestinal disorders. The aim of this study was to investigate the function of gastroenteric neuromusculature and its response to a prokinetic. METHODS: 14 CF children aged 8.6 + 1.3 years were studied by electrogastrography and compared to 10 age-matched controls. A second recording was performed in CF patients after administration of cisapride (0.3 mg/kg). Parameters analyzed were percentage of normal gastric rhythm (2.0 to 4.0 cpm), percentage of tachygastria (4.0 to 9.0 cpm), dominant frequency instability coefficient and power ratio. RESULTS: CF and control groups were not different in age, height or weight. A significant post-prandial increase in percentage of tachygastria (26.7 + 4.5 versus 12.4 + 2.6; P < 0.05) was seen in CF patients, which was not corrected by cisapride. The power ratio showed a statistical increase in 3 cpm (3.7 + 0.8 versus 1.6 + 0.3; P < 0.05) and in tachygastria (5.3 + 1.2 versus 1.7 + 0.4; P < 0.03) in CF compared with controls. Cisapride had an effect on tachygastria power ratio (3.0 + 0.5; P < 0.04). Analysis of normal rhythm and the dominant frequency instability coefficient were not statistically different in CF and controls. CONCLUSION: This study provides evidence of gastric dysmotility in CF patients.

Adolescent↗
PubMed2004

Respiratory viruses and severe lower respiratory tract complications in hospitalized patients.

BACKGROUND: Acute respiratory viral infections are generally self-limited in healthy subjects but can lead to severe complications in immunocompromised hosts. We report the clinical impact of acute lower respiratory tract viral infections in hospitalized patients. MATERIALS AND METHODS: Of 1,001 fiberoptic bronchoscopies performed during a period of 5 years, 33 BAL samples were positive for respiratory viruses by cell culture. The main diagnosis, length of hospitalization, response to initial treatment, and the mortality rate at 30 days were analyzed. Spirometry performed before and after infection was compared in lung transplant recipients. RESULTS: The following respiratory viruses were identified in 33 cases: influenza A or B (n = 13), parainfluenza virus 1-3 (n = 7), rhinovirus (n = 5), respiratory syncytial virus (n = 4), and adenovirus (n = 4). All cases were immunocompromised patients who acquired new respiratory symptoms and/or radiologic abnormalities suggesting a pulmonary infection. Twenty-five patients (74%) did not respond to initial broad-spectrum antibiotics, and 11 patients (33%) required intensive care for respiratory failure. The overall mortality rate at 1 month was 24%. In patients with a sole viral pathogen identified in their BAL, the mortality rate was 39%. In lung transplant recipients (n = 10), the mean FEV(1) decreased from 2.2 to 1.9 L/s before and during the infection episode, respectively (p < 0.01); 3 months later, 60% of the patients had still not completely recovered to baseline values. CONCLUSION: Respiratory viruses recovered in BAL samples of immunocompromised patients are associated with severe lower respiratory complications. In lung transplant recipients, we observed a persisting impairment of pulmonary function.

Acute Disease↗