Radiofrequency electrostimulation of sympathetic nerve boundary trunk in patients with bronchial asthma

In 7 patients aged from 43 to 64 years with severe infectious allergic forms of bronchial asthma with curative aims radiofrequency electrostimulator for the boundary trunk of the sympathic nerve (BTSN) has been implanted in the neck. Daily sessions of electrostimulation (ES) by the current with parameters 1-100 Hz, 0.1-0.4 m/s, 0.1-2.0 V adjusted individually by maximal broncholytic and clinical effects were performed for 5 years. It was established that ES of BTSN can produce both bronchial dilatation and bronchial spasm. Application of ES of BTSN has resulted in a decrease of bronchial hyperreactivity, frequency of asthmatic attacks 2.6-3.2 fold in consumption of antiasthmatic drugs 2.4-2.7 fold. The only complication has been detected--rejection of the electrostimulator due to the defect of its capsule. This method can be applied as an adjuvant in therapy of severe forms of bronchial asthma resistant to drug treatment.     

A novel surgical technique for implanting a new electrostimulation system for treating female overactive bladder: a preliminary report

OBJECTIVE: To assess the results of peripheral electrostimulation of pelvic floor muscles in patients with overactive bladder (OAB) symptoms, and to describe a novel surgical technique for inserting a specially designed implantable electrostimulator which can deliver different forms of muscle stimulation through a para-urethral electrode. PATIENTS AND METHODS: The study included seven women with OAB (mean age 59 years) who had frequency (including nocturia), urgency and urge incontinence for > or = 1 year, and in whom conventional treatment failed. The antepubic technique was used to implant the electrostimulator and a para-urethral electrode. The patients' urinary symptoms and quality of life (King's College Hospital incontinence questionnaire) were compared before and after surgery, and possible complications monitored. RESULTS: The mean (range) follow-up was 14.5 (13-17) months in six and 10 months in the seventh patient (stimulator removed because of infection). The mean (range) frequency of 15 (13-23) voids/24 h before surgery decreased to 9 voids/24 h (i.e. by 40%) afterward. All patients had leakage episodes because of urgency (4-15 times/day) before surgery, which ceased in five afterward; these patients used no further pads. In the remaining two patients urgency incontinence continued after surgery, but with significantly fewer leakage episodes, from 15 and 12 per day before to 6.7 and 4 afterward, respectively. The mean degree of urgency (graded 0-3) decreased from 2 to 1.4 after surgery, and quality of life improved significantly. Urodynamic studies showed a greater mean maximum detrusor capacity, from 135 mL before to 189 mL after implanting the stimulator. CONCLUSIONS: The good results (over a follow-up of 1 year) in patients with OAB symptoms treated by the present electrostimulator should encourage further clinical studies in such patients. A trial to evaluate the efficacy of pelvic floor muscle electrostimulation in a broad spectrum of diseases of the lower urinary tract causing symptoms similar to OAB has been started.     

Incidence of asthmatic attack during anesthesia in patients with a history of bronchial asthma]

We investigated retrospectively, the incidence of intraoperative asthmatic attack in patients with bronchial asthma, and compared the past 5-year period (Jan 1, 1979 to Dec 31, 1983) and the recent 5-year period (July 1, 1990 to June 30, 1994). The influence of anesthetic methods, induction agents, and intervals between the most recent attack and anesthesia were evaluated. The incidence of the attack during anesthesia in patients with asthma was similar in both period, 6.7% in the past and 7.8% in the recent period. Patients who had a history of recurrent attacks within 2 years prior to anesthesia tended to have higher incidence of intraoperative attack in both periods. Furthermore, the incidence of asthmatic attack was significantly greater in patients receiving inhalational anesthetics for induction of anesthesia than in those given intravenous anesthetics in the recent period. Although inhalational anesthetics are considered to be used safely for asthmatic patients, care should be taken when volatile anesthetics are administered to asthmatic patients during induction of anesthesia.     

Childhood factors associated with asthma remission after 30 year follow up

BACKGROUND: Factors contributing to either "complete" or "clinical" remission of asthma are important to know since there is no cure for the disease. METHODS: A cohort of 119 allergic asthmatic children was examined three times with a mean follow up of 30 years. They were aged 5-14 years at visit 1 (1966-9), 21-33 years at visit 2 (1983-6), and 32-42 years at visit 3 (1995-6). Complete remission of asthma at visit 3 was defined as no asthma symptoms, no use of inhaled corticosteroids, normal lung function (FEV1 >90% predicted), and no bronchial hyperresponsiveness (PC10 >16 mg/ml). Clinical remission was defined as no asthma symptoms and no use of inhaled corticosteroids. RESULTS: 22% of the group was in complete remission of asthma at visit 3 and a further 30% was in clinical remission (total 52%); 57% of subjects in clinical remission had bronchial hyperresponsiveness and/or a low lung function. Logistic regression analyses showed that a higher FEV1 in childhood and more improvement in FEV1 from age 5-14 to 21-33 were associated with both complete and clinical asthma remission at age 32-42. CONCLUSIONS: Complete remission of asthma was present in a small subset of asthmatics while half the subjects showed clinical remission. Both complete and clinical remission were associated with a higher lung function level in childhood and a higher subsequent increase in FEV1. These results support the view that defining remission only on the basis of symptoms and medication use will overlook subjects with subclinical active disease and possibly associated airway remodelling.     

Patient-adjusted intermittent electrostimulation for treating stress and urge urinary incontinence

OBJECTIVE: To assess the safety and efficacy of pelvic floor muscle electrostimulation (ES) in women with stress urinary incontinence (SUI) or mixed UI (MUI, urge and interstitial cystitis), using a new portable electrostimulator (Miniaturo, Biocontrol Medical Inc., Yehud, Israel) which delivers different forms of stimulation for treating these two conditions. PATIENTS AND METHODS: For SUI the stimulator is activated on demand only by a sudden increase in intra-abdominal pressure; for frequency and urgency a milder, continuous ES is used. The intensity of ES can be adjusted according to the patient's sensation. Women were enrolled into the study after satisfying inclusion criteria and pad testing; 23 participated in two study groups, i.e. 16 with SUI and seven with MUI (severe frequency, urgency and urge, and mild SUI). The pelvic floor muscles were stimulated through an electrode inserted paraurethrally, positioned similarly in all patients. In patients with SUI and MUI a pressure sensor was also inserted into the rectum, to record intra-abdominal pressure. Stimulation was applied for 1-4 h in patients with SUI and for 6 h in those with MUI. The evaluation was based on urinary symptoms (frequency, urgency, leaking episodes), quality-of-life questionnaires and pad tests at baseline and during stimulation. RESULTS: All patients in both groups improved significantly; of the 16 patients with SUI, nine were completely dry during ES, and the remaining seven had a reduced mean pad weight, from 23 to 6 g (74%). There was no significant reduction in pad weight after sham ES (17 g before vs 24.2 g after). In four patients with SUI who continued ES for 4 h the mean cumulative stimulation time (calculated from the stimulator memory) was 3 min (1.3% of 4 h). In the MUI group there were no leakage episodes during ES and significant reductions in voiding variables (Student's t-test) in all. The mean (Sd) voiding frequency, urinary urgency and leaking episodes decreased from 8.1 (4.2) to 1.9 (1.5), 6.4 (2.3) to 0.7 (1.3) and 2.1 (0.7) to 0.7 (0.5) (all P < 0.001), respectively. CONCLUSIONS: The concept of this ES system for treating UI is promising; this study supports the efficacy of this form of ES but no conclusions about clinical efficacy are possible at this stage, and thus a trial to evaluate the safety and efficacy of this implantable device is ongoing.     

Response of the nose to exercise in healthy subjects and in patients with rhinitis and asthma.

BACKGROUND--Although the nose and the bronchi are both involved in the process of regulating respiratory heat exchange, thermal changes may precipitate airway obstruction during exercise but rarely cause nasal obstruction in patients with rhinitis. The cause of the different response of the nose and bronchial tree has hardly been investigated. This study was performed to assess the response of the nose during exercise in the presence of rhinitis, asthma, and in normal controls. METHODS--Ten healthy subjects (group 1), 15 patients with asthma and rhinitis (group 2), 10 with rhinitis only (group 3), and 11 with asthma only (group 4) were included in the study. Exercise was performed on a bicycle ergometer for six minutes, reaching a heart rate of 80% of predicted. Bronchial and nasal responses were measured by forced expiratory volume in one second (FEV1) and posterior rhinomanometry, respectively. A drop in the FEV1 of 20% or more was considered a positive exercise induced asthma challenge test. RESULTS--Heart rate and ventilation increased by a similar proportion in the four groups. The FEV1 significantly decreased in asthmatic patients (groups 2 and 4) but it did not change in healthy subjects (group 1) or in those with rhinitis (group 3). Thirteen asthmatic patients developed exercise induced asthma. Nasal patency increased with exercise by a similar proportion in all groups, and no differences were detected between those with rhinitis (groups 2 and 3) and those without (groups 1 and 4). Nasal patency had returned to basal values at 25 minutes after completion of exercise in the four groups. The nose of patients with exercise induced asthma, however, remained significantly more patent than in patients without exercise induced asthma between 10 and 30 minutes after exercise. CONCLUSIONS--These results suggest that the nose responds differently from the bronchi during exercise induced airway obstruction: whereas the bronchial tree responds by becoming narrowed, the nose becomes more patent. These findings suggest that the mechanisms regulating the response of the nose to exercise are different from those involved in the response of the bronchial tree.     

Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up

BACKGROUND: Childhood asthma is generally believed to be a disorder with a good prognosis. However, some asthmatics develop irreversible airway obstruction, probably as a result of airway remodelling. METHODS: After 21-33 years, 228 adults (aged 13-44 years at baseline) with a history of asthma were re-examined to assess risk factors for the development of irreversible airway obstruction (IAO, forced expiratory volume in 1 second (FEV(1)) <80% predicted and reversibility <9% predicted) and a reduced postbronchodilator transfer coefficient (carbon monoxide transfer factor/alveolar volume, <80% predicted), both characteristics of COPD. RESULTS: At follow up, 41% did not have airway obstruction (NAO), 43% had reversible airway obstruction (RAO), and 16% had IAO; 23% had a reduced transfer coefficient. Patients with RAO had asthma-like characteristics (wheezing, asthma attacks, bronchial hyperresponsiveness (BHR)) while patients with IAO had COPD-like symptoms (cough, phlegm, dyspnoea) at follow up. The development of IAO is determined by a lower FEV(1), less reversibility of airway obstruction and, surprisingly, less severe BHR at initial screening. Eighty percent of the patients with asthma who used anti-inflammatory medication still had airway obstruction, but IAO developed less frequently. Smoking was associated with a reduced transfer coefficient but not with the development of IAO. Female sex was associated with a reduced transfer coefficient, whereas corticosteroid use was not. CONCLUSIONS: Although IAO and a low transfer coefficient are both characteristics of COPD, they represent distinct entities in adult asthmatics in terms of symptomatology, aetiology, and probably in therapeutic approaches and disease prevention.     

Adenocystic bronchial cancer

Among 4005 patients with lung cancer 26 (0.65%) of them had adenocystic bronchial cancer, including 13 male and 13 female patients aged 13 to 60 years. Overall 33 operations have been performed at 26 patients, 5 of them were operated twice, and 1 patient underwent 3 surgical procedures. The plastic operations on bronchi (10) were the main surgical procedures. Four patients underwent pneumonectomy with resection of tracheal bifurcation, and 2 patients - circular resection of primary bronchus with resection of carine and tracheobronchial angle. One patient died after surgery, postoperative complications were seen at 4 patients including hemothorax (1), bleeding (1) and empyema (2). Twenty-five patients have been discharged, 21 of them were followed-up. Three patients survived more 3 years, 6 patients - more 5 years, 8 - more 10 years, 2 - more 15 years, and 2 - more 20 years. Long-term results of radical surgical treatment argue the efficacy of these surgeries at adenocystic bronchial cancer.     

Increased blood carboxyhaemoglobin concentrations in inflammatory pulmonary diseases

BACKGROUND: Exhaled carbon monoxide has been reported to increase in inflammatory pulmonary diseases and to be correlated with blood carboxyhaemoglobin (Hb-CO) concentration. A study was undertaken to determine whether arterial blood Hb-CO increases in patients with inflammatory pulmonary diseases. METHODS: The Hb-CO concentration in arterial blood was measured with a spectrophotometer in 34 normal control subjects, 24 patients with bronchial asthma, 52 patients with pneumonia, and 21 patients with idiopathic pulmonary fibrosis (IPF). RESULTS: The mean (SE) Hb-CO concentrations in patients with bronchial asthma during exacerbations (n=24, 1.05 (0.05)%), with pneumonia at the onset of illness (n=52, 1.08 (0.06)%), and with IPF (n=21, 1.03 (0.09)%) were significantly higher than those in control subjects (n=34, 0.60 (0.07)%) (mean difference 0.45% (95% confidence interval (CI) 0.23 to 0.67), p<0.01 in patients with bronchial asthma, mean difference 0.48% (95% CI 0.35 to 0.60), p<0.0001 in patients with pneumonia, and mean difference 0.43% (95% CI 0.26 to 0.61) p<0.001 in patients with IPF). In 20 patients with bronchial asthma the Hb-CO concentration decreased after 3 weeks of treatment with oral glucocorticoids (p<0.001). In 20 patients with pneumonia the Hb-CO concentration had decreased after 3 weeks when patients showed evidence of clinical improvement (p<0.001). The values of C-reactive protein (CRP), an acute phase protein, correlated with Hb-CO concentrations in patients with pneumonia (r=0.74, p<0.0001) and in those with IPF (r=0.46, p<0.01). In patients with bronchial asthma changes in Hb-CO concentrations were significantly correlated with those in forced expiratory volume in 1 second (FEV(1)) after 3 weeks (r=0.67, p<0.01). Exhaled carbon monoxide (CO) concentrations were correlated with Hb-CO concentrations (n=33, r=0.80, p<0.0001). CONCLUSIONS: Hb-CO concentrations are increased in inflammatory pulmonary diseases including bronchial asthma, pneumonia, and IPF. Measurement of arterial Hb-CO may be a useful means of monitoring pulmonary inflammation.     

Long-term impact of functional endoscopic sinus surgery on asthma.

Using objective and subjective criteria, we performed a study to assess the long-term impact of functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis and asthma at an average follow-up of 6.5 years. One hundred twenty patients who underwent FESS for chronic rhinosinusitis were followed up for an average of 6.5 years (range 6.0 to 10.6 years). Seventy-two (60%) patients responded to a follow-up questionnaire, and 30 (42%) of them reported a history of asthma. Subjective levels of improvement and assessments of medication need were evaluated and statistically assessed with parametric and nonparametric methods. Of these 30 patients, 27 (90%) reported that their asthma was better than it had been before FESS, 6.5 years ago. Average reported improvement increased from 49% at 1.1 years after surgery to 65% at 6.5 years after surgery. Asthma attacks declined in 20 of 27 (74.1%). Medication use for asthma showed similar improvement, with approximately half reporting less inhaler usage and nearly two thirds reporting less oral steroid use. This study demonstrates that a combination of FESS, careful postoperative care, and appropriate medical therapy for chronic rhinosinusitis has a favorable long-term effect on asthma in patients with symptomatic chronic sinusitis. In this study asthma severity, frequency of attacks, and medication need were all improved.     

Macroscopic and microscopic lesions in bronchial asthma

Bronchial asthma is a chronic inflammatory disease characterized by reversible airways obstruction, inflammation, and increased bronchial hyperresponsivennes. The aim of this study was to evaluate the macroscopic and microscopic airways lesions, using bronhoscopy followed by biopsy in 38 cases of Outpatient Department from Clinic of Pulmonary Diseases Ia?i, investigated between January 2005 - June 2008. Patients distribution according to the degree of severity was performed, using the international recommendations for asthma management of the Global Initiative for Asthma (GINA): intermittent (n=7 patients), mild persistent (n=10 patients), moderate persistent (n=16 patients), and severe persistent (n=5 patients). 23,68% of patients had a chronic disease of more than 15 years. The endoscopic changes of the peripheral airways were represented by edema, congestion, bronchial stenosis and mucus hypersecretion. Microscopic routine exam showed epithelial lesions (epithelial desquamation, goblet cell hyperplasia, squamous metaplasia), basement membrane thickening, edema, increased vascularisation, glandular and muscular hypertrophy and bronchial inflammatory infiltrate. Although bronhoscopy exam offers important information regarding changes of the airway mucosa in bronchial asthma, it concomitantly provide bioptic control, as microscopic examination still represents the "gold standard" assessment of bronchial wall remodeling process.     

Use of olprinone, a phosphodiesterase III inhibitor, in an asthmatic patient

Phosphodiesterase (PDE) III exists in airway smooth muscles. In addition, PDEIII inhibitors have been suggested to relax airway smooth muscle by increasing intracellular cAMP concentrations. We report a successful use of olprinone, a PDEIII inhibitor, for treatment of an asthmatic attack. A 15-year-old male patient treated with oral theophylline 400 mg x d(-1) was anesthetized with propofol, fentanyl and ketamine for knee joint surgery. Immediately after tracheal intubation, an asthma attack occurred with peak airway pressure (Paw)>40 cmH2O. Thus, propofol 20 mg was additionally given to increase anesthetic depth, and Paw gradually decreased to 30 cmH2O. In addition, we started monitoring bronchial cross-sectional area using a superfine fiberoptic bronchoscopic method previously reported. However, as Paw did not further decrease for 30 min, olprinone was intravenously infused (10 microg x kg(-1) x 10 min(-1) + 0.3 microg x kg(-1) x min(-1), total 5 mg). Olprinone infusion rapidly decreased peak Paw from 30 cmH2O to 24 cmH2O and increased bronchial cross-sectional area by 50%. These findings suggest that olprinone produced bronchodilation.     

Comparison of atopic cough with cough variant asthma: is atopic cough a precursor of asthma?

BACKGROUND: We have described a group of patients who present with isolated chronic bronchodilator resistant non-productive cough with an atopic constitution, eosinophilic tracheobronchitis, and airway cough receptor hypersensitivity without bronchial hyperresponsiveness, which we have termed "atopic cough". Although cough variant asthma (in which the cough responds to bronchodilators) is recognised as a precursor of typical asthma, it is not known whether atopic cough is also a precursor of asthma. METHODS: Eighty two patients with atopic cough were retrospectively examined for onset of typical asthma and compared with 55 patients with cough variant asthma (20 untreated patients and 35 treated with long term inhaled beclomethasone dipropionate (BDP), 218-467 micro g/day). The median follow up period for patients with atopic cough and cough variant asthma was 4.8 (1-11.5) years and 3.7 (1-12.4) years, respectively. RESULTS: Onset of typical asthma occurred in only one of the patients with atopic cough. In patients with cough variant asthma, typical asthma developed in two of 35 patients taking BDP and six of 20 untreated patients (difference 24.3%, 95% CI 2.8 to 45.8, p<0.02). CONCLUSIONS: These findings suggest that cough variant asthma is a precursor of typical asthma but that atopic cough is not. Treatment with inhaled steroids may prevent the transformation of cough variant asthma into typical asthma.     

Influence of circulating alpha adrenoceptor agonists on lung function in patients with exercise induced asthma and healthy subjects.

The influence of circulating noradrenaline (in this context primarily a non-selective alpha agonist) and the alpha 1 selective agonist phenylephrine on bronchial tone, blood pressure, and heart rate was studied in eight patients with exercise induced asthma and eight age and sex matched controls. All subjects refrained from taking treatment for at least one week before the trial. The agonists were infused intravenously in stepwise increasing doses of 0.04, 0.085, 0.17, and 0.34 micrograms/kg a minute for noradrenaline and 0.5, 1.0, 2.0, and 4.0 micrograms/kg a minute for phenylephrine. At the highest dose the plasma concentration of noradrenaline was about 30 nmol/l, resembling the concentrations found during intense exercise, and that of phenylephrine was about 400 nmol/l. Both agonists caused dose dependent and similar increases in blood pressure in the two groups. Despite clearcut cardiovascular effects (systolic and diastolic blood pressure increased by about 40-50/25-30 mm Hg), neither agonist altered lung function, as assessed by measurements of specific airway compliance (sGaw), peak expiratory flow (PEF), or end expiratory flow rate, in either group. It is concluded that circulating alpha agonists, whether alpha 1 selective (phenylephrine) or non-selective (noradrenaline), fail to alter basal bronchial tone in patients with exercise induced asthma or in healthy subjects.     

Bronchial hyperresponsiveness in young students of southern China: relation to respiratory symptoms, diagnosed asthma, and risk factors.

A cross sectional study was carried out to determine the prevalence of bronchial hyperresponsiveness and asthma in 3067 students aged 11-17 years in an urban and a rural area of Guangzhou (Canton), China. The methods used included a self administered questionnaire, a histamine bronchial provocation test, and allergen skinprick tests. Bronchial hyperresponsiveness was defined as a 20% fall in FEV1 and peak expiratory flow at a provoking dose of histamine (PD20) less than 7.8 mumol on two occasions four weeks apart. The response rate was 98.0% and 99.2% in the two areas. The prevalence of bronchial hyperresponsiveness was 4.1% and of diagnosed asthma 2.4% in the total population. There were no significant differences in prevalence between the urban and the rural area or between boys and girls. The 11-12 year group had a higher prevalence of bronchial hyperresponsiveness (7.6%) than the older groups. Of the 125 with bronchial hyperresponsiveness, 12.0% were defined as having severe or moderate (PD20 less than 0.8 mumol), 26% mild (0.9-3.2 mumol), and 62% slight bronchial hyperresponsiveness (3.3-7.8 mumol). The severity of bronchial hyperresponsiveness was closely related to diagnosed asthma, wheezing, and cough, though half the students with bronchial hyperresponsiveness were symptom free. The most common allergens were house dust and house dust mite in the city, and hay dust, pollen, and feathers in the rural area. The odds ratios for having respectively slight, mild or moderate, and severe bronchial hyperresponsiveness were 5.9, 21.0, and 30.4 for atopy; 1.9, 1.9, and 7.3 for early respiratory infection; and 3.1, 2.5, and 5.6 for a history of parental asthma.     

Relationship between the acid-induced cough response and airway responsiveness and obstruction in children with asthma.

BACKGROUND: In children with asthma little is known about the direct effect of the bronchoconstrictor and bronchodilator response on the cough threshold, or the relationship between bronchial responsiveness and the cough threshold. A study was undertaken to determine the effect of histamine-induced bronchoconstriction and salbutamol-induced bronchodilatation on the cough threshold in response to inhaled acetic acid, and to examine the relationship between the acetic acid cough threshold and bronchial hyperresponsiveness to histamine in children with asthma. METHODS: Nineteen children with asthma (16 boys) of mean (SE) age 10.6 (0.6) years were enrolled in the study. On day 1 each underwent a histamine inhalation challenge to determine the provocative concentration causing a fall in forced expiratory volume in one second (FEV1) of more than 20% (PC20) as an index of individual bronchial hyperresponsiveness. On day 2 the acetic acid cough threshold was determined before and just after the inhalation of the PC20 concentration of histamine, and then salbutamol (1 mg/m2) was inhaled to relieve the bronchoconstriction. Ten of the 19 patients (eight boys) of mean age 12.2 (0.7) years also tried acetic acid inhalation challenge just after salbutamol inhalation. RESULTS: There was no relationship between the bronchial responsiveness to histamine and acetic acid cough threshold in these patients. The acetic acid cough threshold after histamine inhalation was similar to that before histamine, although FEV1 decreased after histamine. In the 10 patients who also tried acetic acid inhalation challenge after salbutamol the cough threshold did not change. CONCLUSIONS: These findings suggest that acid-induced cough sensitivity and bronchomotor tone are independently regulated in children with asthma.     

Comparison of gel contraction mediated by airway smooth muscle cells from patients with and without asthma

BACKGROUNDS: Exaggerated bronchial constriction is the most significant and life threatening response of patients with asthma to inhaled stimuli. However, few studies have investigated the contractility of airway smooth muscle (ASM) from these patients. The purpose of this study was to establish a method to measure contraction of ASM cells by embedding them into a collagen gel, and to compare the contraction between subjects with and without asthma. METHODS: Gel contraction to histamine was examined in floating gels containing cultured ASM cells from subjects with and without asthma following overnight incubation while unattached (method 1) or attached (method 2) to casting plates. Smooth muscle myosin light chain kinase protein levels were also examined. RESULTS: Collagen gels containing ASM cells reduced in size when stimulated with histamine in a concentration-dependent manner and reached a maximum at a mean (SE) of 15.7 (1.2) min. This gel contraction was decreased by inhibitors for phospholipase C (U73122), myosin light chain kinase (ML-7) and Rho kinase (Y27632). When comparing the two patient groups, the maximal decreased area of gels containing ASM cells from patients with asthma was 19 (2)% (n = 8) using method 1 and 22 (3)% (n = 6) using method 2, both of which were greater than that of cells from patients without asthma: 13 (2)% (n = 9, p = 0.05) and 10 (4)% (n = 5, p = 0.024), respectively. Smooth muscle myosin light chain kinase levels were not different between the two groups. CONCLUSION: The increased contraction of asthmatic ASM cells may be responsible for exaggerated bronchial constriction in asthma.     

Expression and activation of TGF-beta isoforms in acute allergen-induced remodelling in asthma

BACKGROUND: Airway wall remodelling and inflammation are features of chronic asthma. Transforming growth factor beta (TGF-beta) has been implicated in these processes. AIM: To determine the effect of allergen challenge on airway inflammation and remodelling and whether TGF-beta isoforms and the Smad signalling pathways are involved. METHODS: Thirteen patients with atopic asthma underwent inhalational challenge with 0.9% saline, followed by allergen 3-4 weeks later. After both challenges, fibreoptic bronchoscopy was undertaken to obtain bronchial biopsies and tissue samples were processed for immunohistochemistry and examined by microscopy. RESULTS: Forced expiratory volume in 1 s (FEV(1)) fell after allergen challenge (mean (SE) -28.1 (0.9)% at 30 min with a late response at 7 hours (-23.0 (1.2)%). Allergen challenge caused an increase in neutrophils and eosinophils in the bronchial mucosa compared with saline. Sub-basement membrane (SBM) thickness did not change after allergen, but tenascin deposition in SBM was increased. Intranuclear (activated) Smad 2/3 and Smad 4 detected by immunohistochemistry were increased after allergen challenge in epithelial and subepithelial cells of bronchial biopsies. No inhibitory Smad (Smad 7) protein was detected. TGF-beta isoforms 1, 2 and 3 were expressed predominantly in bronchial epithelium after saline and allergen challenges, but only TGF-beta(2) expression was increased after allergen. Double immunostaining showed an increase in TGF-beta(2) positive eosinophils and neutrophils but not in TGF-beta(1) positive eosinophils and neutrophils after allergen challenge. CONCLUSIONS: TGF-beta(2) may contribute to the remodelling changes in allergic asthma following single allergen exposure.     

Outcome of surgery for failed endoscopic extraction of common bile duct stones in elderly patients.

Endoscopic sphincterotomy (ES) is the treatment of choice for common bile duct stones in elderly patients. For those in whom endoscopic clearance of the common bile duct fails the treatment options include stenting, dissolution therapy and lithotripsy. Surgery is often avoided because of the reported high morbidity and mortality in elderly patients. We have reviewed the outcome of patients referred for surgery after failed endoscopic clearance of common bile duct stones. Over a 3-year period, 100 patients with common bile duct stones were referred specifically for endoscopic clearance of the common bile duct (median age 69 years, range 19-97 years). In seven patients duct clearance was possible without ES and in five patients ES was considered inappropriate. ES was attempted in 88 patients and was successful in 75 (85%). Of the 13 patients failing ES or stone removal, surgery was performed in nine and four were stented. Of patients having successful ES (n = 75), ten were referred for surgery because of incomplete duct clearance. Surgery was performed to obtain duct clearance in 19 patients (eight male, 11 female, median age 77 years, range 47-90 years). Of the 19, eight had previously undergone a cholecystectomy (42%) and 17 of the 19 had biliary tract drainage preoperatively (90%). The procedures performed consisted of choledocholithotomy in all plus cholecystectomy (11), choledochoduodenostomy (7) and choledochojejunostomy (7). There were no deaths and only one major complication. The median total inpatient stay was 26 days (range 14-75 days) and the median postoperative stay was 12 days (range 7-50 days). We would conclude that open surgery can be performed safely and effectively in elderly patients with retained bile duct stones.     

Increase in diagnosed asthma but not in symptoms in the European Community Respiratory Health Survey

BACKGROUND: Information on the epidemiology of asthma in relation to age is limited and hampered by reporting error. To determine the change in the prevalence of asthma with age in young adults we analysed longitudinal data from the European Community Respiratory Health Survey. METHODS: A self-administered questionnaire was completed by 11 168 randomly selected subjects in 14 countries in 1991-3 when they were aged 20-44 years and 5-11 years later from 1998 to 2003. Generalised estimating equations were used to estimate net change in wheeze, nocturnal tightness in chest, shortness of breath, coughing, asthma attacks in the last 12 months, current medication, "diagnosed" asthma, and nasal allergies. RESULTS: Expressed as change in status per 10 years of follow up, subjects reporting asthma attacks in the previous 12 months increased by 0.8% of the population (95% CI 0.2 to 1.4) and asthma medication by 2.1% (95% CI 1.6 to 2.6), while no statistically significant net change was found in reported symptoms. Reported nasal allergies increased, especially in the youngest age group. CONCLUSIONS: As this cohort of young adults has aged, there has been an increase in the proportion treated for asthma but not in the proportion of those reporting symptoms suggestive of asthma. Either increased use of effective treatments has led to decreased morbidity among asthmatic subjects or those with mild disease have become more likely to label themselves as asthmatic.