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[Pharmacology of mucociliary transport].

Muco-ciliary transport is only effective because of the coordination of the ciliary beats (metachronous) and the harmony between mucus and cilia. The tip of the cilia is in contact with a jellyform layer of mucus propelled to the oropharynx. This jellyform layer has a complex rheological behaviour: it flows like a liquid and shapes like solid elastic. When the rheological properties of bronchial secretion are abnormal, mucociliary transport becomes inefficient. However, the most fluid secretions are not necessarily best transported, because the elasticity and viscosity to guarantee efficient muco-ciliary transport can only vary within defined limits. The mechanism regulating the ciliary beats is poorly understood; the bronchial secretions conduct impulses through the autonomic nervous system as well as mediators such as histamine and the metabolites of arachidonic acid. Mucociliary function may be studied either, directly through mucociliary transport or through mucociliary clearance. A fall in mucociliary activity can be produced by a primary ciliary disorder, by bronchial disease or the consequences of respiratory infection. General anaesthetics and Atropine slow mucociliary transport but Ipratropium bromide does not; Theophylline and sympathomimetics speed it up. The expectorants are mucolytics (proteolytic enzymes, N-acetyl-cysteine), there are agents to correct hydration anomalies of the bronchial secretion (water, hypertonic sodium chloride) iodides, antifibrins by substitution, anti-inflammatory agents and mucoregulatory agents (S-carboxymethylcysteine, bromhexine). The efficacy of the greater part of these expectorants has not been established in vivo by controlled therapeutic trials.

Anesthetics↗

Therapeutic approaches to the common cold in children.

In a five-day, randomized, double-blind study, the efficacy and safety of a syrup containing a combination of azatadine maleate, pseudoephedrine sulfate, and dextromethorphan hydrobromide (SCH 399 syrup) were compared with those of an expectorant containing the antihistamine diphenhydramine hydrochloride in 60 children with symptoms of the common cold and associated cough. One-half teaspoonful of assigned medication was administered three or four times daily. The severity of signs and symptoms was graded on days 0, 3, and 5. At days 3 and 5, patients treated with SCH 399 experienced a significantly greater degree of relief (P less than 0.001) than did patients treated with the expectorant product. Differences between treatment groups in overall therapeutic response, as evaluated by the physician, were statistically significant (P less than 0.001) at each visit, favoring patients treated with SCH 399. More than 75% of the patients treated with SCH 399 demonstrated an excellent therapeutic response. Tolerance to both study medications was excellent.

Antitussive Agents↗

[Effect of brovanexine on secretory activities of tracheal secretory cells].

The expectorant effect of brovanexine (BvX) was investigated histologically and histochemically using isolated canine trachea. Following BvX treatment, the number of goblet cells (GC) stained positively with the combination procedure of alcian blue at pH 2.5 or pH 1.0 and periodic acid-Schiff was unaffected. The number of GC which stained blue and purple (stain index B & P) was reduced, while the number of GC that stained red (stain index R) was increased. The thickness of the acini of submucosal glands (SG) markedly decreased with 10(-5) and 10(-4)M BvX, and the ratio of the acinar inner diameter to the tracheal wall thickness significantly increased with 10(-4)M BvX. Stain index B & P of glandular cells decreased with 10(-5) and 10(-4)M BvX, which was accompanied by a marked increase in the stain index R. BvX treatment caused increases in total saccharide and protein concentrations in the incubation fluid, while N-acetylhexosamine slightly decreased. Both the BvX-induced histological changes in glandular cells and changes in concentrations of macromolecular components in the incubation fluid were much the same degree as those induced by bromhexine (Bh). The BvX-induced histochemical changes in secretory cells, however, were slighter than those induced by Bh. These findings suggest that BvX is an expectorant possessing both the secretagogic action selectively on SG and a mucolytic action toward acid glycoproteins in granules of secretory cells.

Animals↗

[Clinical evaluation of efficacy and tolerance of oral treatment with ambroxol in patients with chronic bronchitis].

This study was designed to examine the efficacy and tolerability of ambroxol (Ambrosol) on the symptomatology of chronic bronchitis among in- and out-patients. Seventy patients were included in the trial and divided into two random groups. The patients were treated in a double-blind way with either Ambrosol or a placebo for 2 months. The physician and the patient assessed the following points: the feeling general well-being, the symptoms of a cold and of fever, the need for treatment with antibiotics, the amount, viscosity and colour of sputurn, the difficulty in expectoration, the severity of coughing and any changes in breathlessness while at rest. In order to carry out these subjective assessments we used a scoring system. We observed that, breathlessness while at rest and the rate of exacerbation was significantly lower in the Ambrosol group after 2 weeks of therapy. Sputum viscosity, difficulty in expectoration and severity of coughing were reduced in this group after 4 or 8 weeks. Throughout the 2-month period of therapy, the tolerability of ambroxol was good. A total of 4 patients reported side-effects of various degrees of severity. One patient stopped the therapy due to these side-effects (dizziness). There was no significant difference in the number of side-effects between the two groups (Ambrosol vs Placebo).

Administration, Oral↗

[Pharmacological comparative study on baiqian and baiwei].

The decoction of Cynanchum glaucescens and the ethanol extract of C. stauntonii show significant antitussive and expectorant actions. The decoctions of C. stauntonii or C. glaucescens have antiasthmatic and anti-inflammatory effects. The decoction of C. atratum has some expectorant effect but no antitussive or antiasthmatic actions. On the other hand, the decoction of C. versicolor cannot relieve cough nor sputum. The results indicate that both C. atratum and C. versicolor cannot be used as C. glaucescens or C. stauntonii.

Adolescent↗

A comparison of bronchial drainage treatments in cystic fibrosis.

We compared standard chest physical therapy and postural drainage (CPT/PD) with a new airway clearance therapy called high-frequency chest wall oscillation (HFCWO) in a group of stable cystic fibrosis (CF) patients. In this crossover trial, 29 CF patients (15 males, 14 females), aged 7-47 years that met the inclusion criteria were randomly assigned to alternate CPT/PD and HFCWO, on a daily basis, over a 4 day period. Each patient received 2 days of each form of therapy; treatment frequency and the length of treatment were the same for both techniques. Expectorated secretions were collected during each 30 minute therapy session and for 15 minutes following treatment. The wet and dry weights of collected secretions were determined gravimetrically, and the therapy methods were compared. Significantly more sputum was expectorated during HFCWO than during CPT/PD as determined by both the wet (P < 0.001) and the dry (P < 0.01) measurements. This study suggests that HFCWO is at least as effective as manual CPT/PD in clearing secretions from the airways in patients with cystic fibrosis.

Adolescent↗

Non-invasive ventilation for cystic fibrosis.

BACKGROUND: The use of non-invasive ventilation (NIV) has been proposed as a means to temporarily reverse or slow the progression of worsening respiratory failure in cystic fibrosis (CF). OBJECTIVES: To compare the effect of NIV versus no NIV in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. The reference lists of each trial were searched for additional publications that may contain other trials. Date of most recent search: January 2002. SELECTION CRITERIA: Relevant randomised controlled trials in which a form of pressure preset or volume preset NIV versus no NIV was used in people with acute or chronic respiratory failure in CF. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion criteria, methodological quality and data extraction. MAIN RESULTS: Six trials were identified and four trials met the inclusion criteria with a total of 55 participants. All of these trials only evaluated single treatment sessions. Two trials (36 participants) evaluated the use of NIV for airway clearance compared with an alternative physiotherapy method. These trials showed that airway clearance may be easier and people with CF may prefer to use NIV for airway clearance. There was no evidence that NIV increases sputum expectoration or improves lung function. Two trials (19 participants) evaluated the use of NIV for overnight ventilatory support. Of the primary outcomes examined in this review, only lung function was evaluated within the two trials. Due to the small numbers of participants and the differing statistical techniques used within the review and the primary trials, there were discrepancies in the results obtained by the RevMan analysis and the original trial analysis. No clear differences were found between NIV compared with either oxygen or room air. REVIEWER'S CONCLUSIONS: Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with CF who have difficulty expectorating sputum. Non-invasive ventilation when used in addition to oxygen may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of NIV have only been demonstrated in single treatment sessions and its efficacy, safety and acceptability in the longer term are unknown. There is a need for long-term randomised controlled trials to determine the clinical effects of non-invasive ventilation in CF.

Cystic Fibrosis↗

Safety and use of sputum induction in children with cystic fibrosis.

We assessed the safety and use of induced sputum (IS) in children with cystic fibrosis (CF). Forty-eight children (19 males) with CF, mean age 12.6 (range, 7.3-17.0) years and median forced expired volume in 1 sec (FEV(1)) 48% (range, 14-77%) predicted were recruited. Patients spontaneously expectorated sputum and then performed sputum induction by inhalation of nebulized 7% hypertonic saline. Samples were sent for bacteriological culture, and for measurement of the following inflammatory mediators: interleukin-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase activity. FEV(1) was performed before and after inhalation of hypertonic saline. There was no increase in mediator levels in IS compared to expectorated sputum (ES) samples. Only 3 patients demonstrated significant bronchoconstriction following inhalation of hypertonic saline, by the method used. From the ES samples, Pseudomonas aeruginosa was isolated in 13 patients, Staphylococcus aureus in 7 patients, Stenotrophomonas maltophilia in 1 patient, and both Pseudomonas aeruginosa and Staphylococcus aureus in 5 patients. All these organisms were found in the IS samples. However, in 2 patients whose ES grew no organisms, one patient's IS grew Pseudomonas aeruginosa, and the other patient's IS grew Staphylococcus aureus. In our study, sputum induction was safe, with no proinflammatory effect.

Adolescent↗

Nutritional implications of the cephalic-phase reflexes: endocrine responses.

Cephalic phase hormonal release occurs through activation of vagal-efferent fibers in response to food-related sensory stimuli. Thus, tasting, chewing and expectorating food elicits hormonal release prior to nutrient absorption. Differential sensitivity of cell types within the islet to neural activation determines the profile and magnitude of hormonal release. While the magnitude of cephalic phase insulin release is relatively small (25% above baseline), pancreatic polypeptide, a hormone almost exclusively under vagal control increases 100% above baseline when individuals taste, chew and expectorate food. Thus, the cephalic phase pancreatic polypeptide response is a sensitive indicator of vagal activation to food stimuli. The physiological significance of the cephalic phase hormonal responses is demonstrated by experimental manipulations which inhibit or bypass cephalic phase insulin release. Under these circumstances, hyperglycemia and hyperinsulinemia are evident. Conversely, supplementation of insulin during the preabsorptive time period improves glucose tolerance in certain clinical populations. These data suggest that cephalic phase insulin release plays a role in glucose homeostasis.

Animals↗

Effect of the mucoregulator S-carboxy-methyl-cysteine in patients with chronic bronchitis.

Twenty patients with stable chronic bronchitis entered a double-blind study in which changes in clinical and respiratory function and biochemical and rheological variations were examined after treatment with the mucoregulator S-carboxy-methyl-cysteine (S.C.M.C.). After one week of single-blind placebo, a two week double-blind study was initiated with placebo or oral S.C.M.C. 3 g/24h. After two weeks, a significant clinical improvement was observed in patients treated with S.C.M.C. During treatment, there was no change in respiratory function, although a drop in FEV1/VC was noted in the placebo group. A significant increase in the viscosity of the expectorations was observed after treatment with S.C.M.C. for two weeks. The levels of secretory IgA and of serum albumin in the expectorations remained stable, whereas in the placebo group, there was a slight but significant increase in serum albumin. In this group of non-infected chronic bronchitic patients, S.C.M.C. appeared to normalize the secretory function of the bronchial mucosa by preventing inflammation and enhancing the viscoelastic properties of bronchial secretions.

Aged↗

Early small cell lung cancer with extensive inflammation and scar formation.

A 56-year-old man, at one year before his first visit to our hospital, had presented cough, stridor and chest pain, and expectorated a mass, resulting in prompt disappearance of the symptoms. He was afflicted with recurrent symptoms, and the bronchoscopy showed a polypoid tumor occluding the right lower bronchus. The tumor was resected via bronchoscopy, which revealed histologically small cell carcinoma with significant inflammation and scar formation. The tumor was macroscopically the same as the one that had been expectorated by the patient at one year previously. A right lower lobectomy was conducted, but the specimen demonstrated no residual tumor. Tumor invasion into the bronchial wall was therefore limited within the submucosal layer for more than a year. Finally, the present tumor was diagnosed as an early small cell lung cancer with a characteristic of self involution. With no adjuvant treatment, the patient is well without tumor recurrence at 3 years to date after the surgery.

Bronchoscopy↗

Implementation of the Vienna Hydrotherapy Group for Laryngectomees--a pilot study.

GOALS: Laryngectomy involves several problems for the individual, such as the need to cope with a stoma, adjustment to tracheostomal breathing, and the formation of a voice. Contact with water, resulting in aspiration, may prove fatal for laryngectomized patients in the absence of appropriate aids. The aim of this pilot study was to conduct a hydrotherapy group for laryngectomized patients and to evaluate its feasibility and outcome in relation to the goals of therapy. PATIENTS AND METHODS: Six male patients who had undergone laryngectomy were included in a pilot study. The patients underwent a structured hydrotherapy rehabilitation program (three times a week for 8 weeks), using a special underwater therapy device. The patients' posture was controlled by posturography and their endurance capacity by standard ergometry and the 6-min walk. The parameters of fatigue, expectoration, mobility, elasticity/flexibility, postural control/coordination, and general well being were registered on a visual analog scale (VAS). Quality of life was assessed by having the patients fill out the German version of the SF-36 Health Survey. MAIN RESULTS: Posturograpy findings showed an improvement of two subtests ( p<0.028). Exercise testing showed an improved endurance capacity ( p<0.028). The patients were able to walk a greater distance in the 6-min walking test ( p<0.028). The VAS also showed an improvement of endurance capacity ( p<0.028), fatigue ( p<0.028), expectoration ( p<0.043), mobility of the neck and shoulder ( p<0.027), flexibility ( p<0.027), postural control and coordination ( p<0.028), and general well being ( p<0.028). On the SF-36 Health Survey, the patients were improved in the items "Physical functioning" ( p<0.027), "Vitality" ( p<0.027) "Role-physical" ( p<0.026), and "Social functioning" ( p<0.043). CONCLUSIONS: A hydrotherapy group for laryngectomized patients proved to be safe, feasible, and effective in this pilot study.

Activities of Daily Living↗

Clinical study of an outbreak of Legionnaire's disease in Alcoy, Southeastern Spain.

The aim of this study was to identify the clinical features of Legionnaires' disease, sudden outbreaks of which demand a quick and flexible clinical approach, particularly with regard to diagnosis and therapy. A prospective and comparative study based on a clinical protocol was performed during an outbreak of Legionnaires' disease in Alcoy, Spain. The outbreak was environmental in origin, linked to cooling towers. Data about epidemiological and clinical features, blood chemistry values, radiological and microbiological findings, and characteristics related to the clinical course of Legionnaires' disease were obtained for 357 patients admitted to hospital with community-acquired pneumonia (177 with Legionella pneumonia). Patients with Legionnaires' disease were younger (mean age, 65.3+/-16.5 years) and more likely to be smokers compared with patients with other types of pneumonia (28.8% vs. 11.1%; P<0.01). Moreover, they had not been admitted to any hospital because of pneumonia in the previous year. Patients with Legionnaires' disease had higher fever, more severe headache, and less expectoration as well as lower sodium blood levels (mean, 132.6+/-4.8 mmol/l vs. 135.7 mmol/l; P<0.01). Radiological studies also showed that fewer patients with Legionnaires' disease had pleural effusion (9% vs. 19.4% of those with non- Legionella pneumonia). The presence of headache, high fever, hyponatremia, scanty or null expectoration, and current cigarette smoking provides physicians with important clues for a high suspicion of Legionella pneumonia before the results of confirmatory laboratory tests are available.

Adult↗

Sputum induction for the diagnosis of pulmonary disease in HIV positive patients.

We prospectively compared sputum induction with bronchoalveolar lavage (BAL) in HIV positive patients presenting with acute respiratory episodes and also assessed the effects of using an experienced respiratory physiotherapist on the diagnostic yield from induced sputum. One hundred and fifty-one consecutive patients underwent sputum induction, in 96 the procedure was supervised by nursing and medical staff with no specific expertise (group I); in 55 patients a physiotherapist supervised sputum induction (group 2). Nine patients refused BAL having undergone sputum induction. Of the remaining 142 patients sputum induction failed (no sample expectorated) in 28 patients (25 from group 1 and three from group 2), the sample was inadequate (the material expectorated was not from the lower respiratory tract) in 29, and was adequate in 85 patients. Pneumocystis carinii was diagnosed in 82 patients (51 from group 1 and 31 from group 2). The sensitivity of induced sputum for the diagnosis of P. carinii was 13% and of BAL was 77%. In the subgroup of patients with an adequate induced sputum sample, the sensitivity of induced sputum was 28% and of BAL was 73%. Of the remaining 60 patients, 27 had other diagnoses made by induced sputum and BAL (eight patients), BAL only (15 patients) and induced sputum only (four patients). Eleven patients had bronchitis and responded to oral antibiotics. In 22 patients induced sputum and BAL were negative; alternative diagnoses were established by lung biopsy or by culture of blood, urine or CSF. During sputum induction, 15 patients had nausea and vomiting, eight became dyspnoeic, three had intractable cough and one developed acute bronchoconstriction; 17 patients found the procedure unpleasant. Compared with BAL, induced sputum has a lower diagnostic yield for P. carinii and other pathogens. Use of experienced, dedicated personnel increases the number of successful attempts at sputum induction but does not increase the diagnostic yield. Fibreoptic bronchoscopy and bronchoalveolar lavage remain necessary for patients with negative results from induced sputum and those whose disease course is at variance with the diagnosis made by sputum induction.

Acquired Immunodeficiency Syndrome↗

Additive effect of continuous low-dose ofloxacin on erythromycin therapy for sinobronchial syndrome.

It has been established that long-term low-dose erythromycin therapy (EM therapy) is very effective for sinobronchial syndrome, a common condition in Japan characterized by chronic upper and lower airway inflammation. The effect does not result from its bacteriocidal activity and the detailed mechanisms are not known. It takes 3-6 months for EM therapy to improve the symptoms. This study was designed to evaluate the additive effect of continuous low dosage or intermittent usual dosage of ofloxacin (OFLX) on EM therapy in patients with sinobronchial syndrome. Patients with sinobronchial syndrome were randomly allocated to receive one of the following four regimens. Patients in Group A received both low-dose OFLX and EM therapy daily for 6 months. Patients in Group B received EM therapy and intermittent treatment of OFLX for 6 months. Patients in Group C underwent EM therapy for 6 months. Patients in Group D received neither OFLX nor EM therapy. All patients were given carbocystein for more than 2 months before starting each treatment and during the study period. In patients receiving OFLX and/or EM therapy, these antimicrobial agents were well-tolerated during the treatment period. Amount of sputum in the morning was significantly less in Group C than in Group D after 3-6 months, and decreased significantly in Group A as compared with Group B after 2 weeks, Group C after 2 weeks to 2 months, and Group D after 2 weeks to 6 months. Other symptoms such as number of expectorations, difficulty of expectoration and severity of cough also improved rapidly in Group A. These findings suggest that it is useful to add low-dose OFLX to EM therapy for sinobronchial syndrome, especially within 1-2 months from starting treatment, and it may be cost-effective as this combination therapy can shorten the treatment period of EM therapy.

Adult↗

The use of sputum induction for establishing a diagnosis in patients with suspected pulmonary tuberculosis in Malawi.

SETTING: There has been a marked increase in notified cases of smear-negative pulmonary tuberculosis in Malawi since 1986. One reason for this may be related to the difficulties of getting adequate samples of expectorated sputum from patients. Sputum induction with nebulized hypertonic saline may be a simple way of obtaining a better specimen. OBJECTIVE: To examine the value of sputum induction for detecting cases of smear-positive tuberculosis. DESIGN: Sputum induction was performed on 82 adults presenting to the Queen Elizabeth Central Hospital, Blantyre, Malawi with clinically suspected pulmonary tuberculosis who were expectorated sputum smear-negative or unproductive of sputum. The induced sputum smear was examined for acid-fast bacilli and cultured for mycobacteria. RESULTS: Sputum was successfully induced from 73 of the 82 patients (26 previously smear-negative and 47 previously unproductive). The induced sputum was smear-positive in 18 patients (5 previously smear-negative and 13 unproductive). Cultures were positive for Mycobacterium tuberculosis in the 18 smear-positive patients and a further 12 that had been smear-negative. 94 cases of smear-positive pulmonary tuberculosis were notified during the study period. 18 (19%) were as a result of sputum induction. CONCLUSION: Sputum induction is a useful technique for improving the case detection rate of smear-positive tuberculosis in Malawi.

Adolescent↗

Analysis of Delta9-tetrahydrocannabinol in oral fluid samples using solid-phase extraction and high-performance liquid chromatography-electrospray ionization mass spectrometry.

An analytical method using solid-phase extraction (SPE) and high-performance liquid chromatography-mass spectrometry (LC-MS) has been developed and validated for the confirmation of Delta(9)-tetrahydrocannabinol (THC) in oral fluid samples. Oral fluid was extracted using Bond Elut LRC-Certify solid-phase extraction columns (10 cm(3), 300 mg) and elution performed with n-hexane/ethyl acetate. Quantitation made use of the selected ion-recording mode (SIR) using the most abundant characteristic ion [THC+H(+)], m/z 315.31 and the fragment ion, m/z 193.13 for confirmation, and m/z 318.00 for the protonated internal standard, [d(3)-THC+H(+)]. The method proved to be precise for THC, in terms of both intra-day and inter-day analyses, with coefficients of variation less than 10%, and the calculated extraction efficiencies for THC ranged from 76 to 83%. Calibration standards spiked with THC between 2 and 100 ng/mL showed a linear relationship (r(2)=0.999). The method presented was applied to the oral fluid samples taken from the volunteers during the largest music event in Portugal, named Rock in Rio-Lisboa. Oral fluid was collected from 40 persons by expectoration and with Salivette. In 55% of the samples obtained by expectorating, THC was detected with concentration ranges from 1033 to 6552 ng/mL and in 45% of cases THC was detected at concentrations between 51 and 937 ng/mL. However, using Salivette collection, 26 of the 40 cases had an undetectable THC.

Adolescent↗

Thoracic rupture of hepatic hydatidosis (123 cases).

BACKGROUND: Hydatid disease is frequently endemic in countries with poor environmental sanitation and in geographic areas where interaction between humans and animals is common. Pulmonary complications result from the proximity of hydatid cysts in the liver and the diaphragm. METHODS: The medical records of 123 patients, with established hydatid disease manifesting abnormal chest roentgenograms, were retrospectively analyzed for the period January 1990 to December 1999. RESULTS: Chest roentgenogram and abdominal ultrasound provided a correct preoperative diagnosis in 108 patients (87.8%). Expectoration of bile, demonstration of fistula by ultrasound, expectoration of cyst contents, and additional ultrasound or imaging findings were the criteria used to establish the preoperative diagnosis. The remaining 15 cases were confirmed at operation. Men outnumbered women nearly 3:1. Mean age was 36.2 years. Pulmonary resection was performed in 67 cases. Sixty-eight patients presented with a bronchobiliary fistula (55.3%). Morbidity rate was 14.6% and mortality rate was 8.9%. CONCLUSIONS: Thoracotomy offers adequate simultaneous access to both the chest and hepatic lesions with acceptable morbidity and mortality. Endoscopic sphincterotomy undertaken preoperatively is useful in reducing biliary complications.

Adolescent↗