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[Pharmacological effects of brovanexine hydrochloride (BR-222) on the respiratory tract system, particularly on the respiratory tract fluid, mucociliary transport and cough].

Pharmacological effects of brovanexine hydrochloride (BR-222), a new expectorant, on the respiratory tract system was studied in comparison with that of bromhexine hydrochloride. 1. When doses ranging from 5 to 40 mg/kg of BR-222 were given orally (p.o.) or intraduodenally (i.d.) to rats, rabbits and dogs, it caused a significant increase in the output volume of respiratory tract fluid (RTF). It was almost as potent as bromhexine, but its pattern of increasing RTF was different from that of bromhexine. The increase in the serous ingredient of RTF after BR-222 administration seemed to be more remarkable than that after bromhexine treatment, though both drugs had no influences on the component ratio of glucose or protein in the RTF of dogs. 2. BR-222 at 10 and 20 mg/kg (i.d.) showed a tendency to reduce the viscosity of RTF in anesthetized dogs and so did bromhexine. A dose of 10 mg/kg (i.d.) of BR-222 also showed a tendency to reduce the viscosity of sputum obtained from the SO2-exposed rabbits. 3. A dose of 6 mg/kg (i.m.) of BR-222 caused a significant increase in the mucociliary transport rate in unanesthetized pigeons; in contrast with this, bromhexine caused a slight decrease. 4. Both drugs given orally showed no antitussive effects when examined by the "coughing dog" method.

Animals↗

[Clinical and functional effects of domiodol and sobrerol in hypersecretory bronchopneumonias].

A double-blind study has been carried out in adult patients suffering from acute and chronic bronchitis, and acute exacerbation of chronic hypersecretory bronchitis, excluding the bronchorreic forms, in order to evaluate the mucolytic activity of orally given domiodol and sobrerol. Treatment with both drugs resulted in an improvement in the subjective measures of ease of expectoration, severity of coughing and sputum consistency; however, there was no improvement in respiratory functions. Moreover, domiodol resulted in a significant increase in sputum volumes, since the very first days of treatment.

Adult↗

[Clinical trial of a Plantago major preparation in the treatment of chronic bronchitis].

Plantago major, according to literature data, has expectorant, antiphlogistic, pain-relieving effect. The experimental studies confirmed a spastic effect upon the smooth musculature of bronchi as well. Twenty five patients with chronic bronchitis were examined, with or without spastic character, with light and moderately severe deviations in ventilation indices. The treatment period was 25-30 days. A rapid effect on subjective complaints and objective findings was obtained in 80 per cent. Some indices of external respiration were favourably affected. The preparation is with a good tolerance, with no toxic effect on gastrointestinal tract, liver, kidneys, hemopoiesis.

Adult↗

Effects of Varidase buccal tablets on the sputum.

Samples of sputum were collected from ten patients with chronic respiratory diseases following treatment with Varidase (streptodornase and streptokinase) buccal tablets, four tablets per day for a period of seven days, and were compared with specimens obtained before the therapy in terms of rheological and cytochemical parameters. The study revealed a tendency for the respiratory secretion to show a lowered yield point and a decrease in mucous fibers after the therapy, thus suggesting, to some extent, the efficacy of the drug as an expectorant.

Adult↗

Acute exacerbations of chronic bronchitis: focusing management for optimum results.

Acute exacerbations of chronic bronchitis can be recognized clinically by (1) increased cough and dyspnea, (2) a change in character of sputum, and (3) an increase in quantity of sputum. Routine chest radiographs are probably not warranted in initial evaluation. Therapy is aimed at control of inflammation, infection, bronchoconstriction, and mucin production. Corticosteroids improve flow rates in patient with respiratory insufficiency. Antibiotic therapy appears to decrease hospital stay and improve flow rates in patients with bacterial infection, as determined by sputum examination or the presence of two of the following symptoms: increased dyspnea, increased sputum production, purulent sputum. Gram's stain of expectorated sputum often allows targeted and cost-effective therapy. Ipratropium bromide (Atrovent) is the bronchodilator of choice; concomitant use of beta agonists has additional benefit. Research on future therapy may focus on the role of corticosteroids, mucolytic agents, and drugs that counteract the effects of neutrophil elastase. Smoking cessation is the first step in prevention. Antibiotic prophylaxis is warranted only in patients with four or more exacerbations per year. Pneumoccoccal and influenza vaccinations are effective and safe; unfortunately, they are underutilized at present.

Antibiotic Prophylaxis↗

[Effects of long term oxygen therapy in patients with idiopathic pulmonary fibrosis. I. Effect on the course of the primary disease and on pulmonary circulation].

The study was performed in 18 patients (15 F and 3-M) aged 35-57 yers (mean 46 +/- 7) diagnosed as idiopathic lung fibrosis. Ten patients (group A) recived standard treatment (prednisone 10-15 mg/day) and supplementary home oxygen therapy (mean 16.4 h/day) for a period of 4 years. During exacerbations antibiotics, theophylline and expectorants were prescribed. Eight patients (group B) receiving the same treatment without home oxygen, served as controls. At study entry lung function test (TLC, VL, Dlco), blood gases, hematocrit, hemodynamic parameters of the pulmonary circulation and thermodilution cardiac output were measured in all patients. The measurements were repeated after 4 years of follow-up. At follow-up examination no differences in pulmonary function parameters were shown between the groups. Mean pulmonary artery pressure and pulmonary vascular resistance were significantly lower in patients receiving home oxygen therapy (group A) as compared with those treated pharmacologically only (group B). Best effects of oxygen therapy were observed in patient with lower pulmonary artery pressures at study entry.

Adult↗

[Nursing study of supporting aerosolized oxygen by combined drug liquid in children with intensive pneumonia].

148 cases of critical pneumonia at the same period were divided into two groups randomly and supplied by two oxygen therapeutic methods. The study group has 75 cases, whom were given aerosolized oxygen with antibacterial, antiphlogistic drugs, expectorants, antispastic and antiasthmatic drugs, and compared with 73 cases of convenient simple with aerosolized oxygen inhalation. The results showed the frequency, time and starting effect time of inhaling oxygen in two groups have significant difference (P < 0.001) and the alteration of SaO2 and the therapeutic effect in two groups also have significant difference (P < 0.05, P < 0.005 respectively). The total effectual rates of the study and control group were 94.66% and 73.94% respectively. The difference between the duration of hospitalization and the therapeutic expenditure in two groups were significance (P < 0.01, P < 0.05 respectively). The study indicated that aerosolized oxygen combined drug liquid is a better oxygen therapy method for treating pneumonia.

Administration, Inhalation↗

Which cough mixture?

BACKGROUND: Coughing is a defence mechanism to clear the airways but if it becomes ineffective, excessive or persistent it may cause fatigue and impair body function as well as create social problems for the patient. OBJECTIVE: Numerous preparations are available for the alleviation of cough, many containing multiple ingredients including antitussives, expectorants, mucolytics and decongestants. Their modes of action are examined and evidence for their usefulness in treating various types of cough evaluated. DISCUSSION: The use of various preparations in non-productive cough, drug induced cough and productive cough are discussed.

Antitussive Agents↗

Tuberculosis. Clinical aspects and diagnosis.

The presentation of tuberculosis is variable depending on the severity of the infection, the age of the patient, whether the infection is primary or secondary, and whether the manifestations are due to inhalation of organisms or hematogenous dissemination. A definitive diagnosis is made by culture of the organism; spontaneously expectorated sputum is the most suitable specimen for diagnosing pulmonary tuberculosis. Diagnosis of extrapulmonary tuberculosis frequently requires tissue biopsy. The classic staining method for demonstrating tubercle bacilli is the Ziehl-Neelsen technique. Newer methods based on fluorescent dyes and phase-contract microscopy make rapid screening feasible, but false-positive identification is more frequent. Culture of tubercle bacilli is most successful when two media are used. The differential diagnosis of pulmonary tuberculosis includes bacterial pneumonia, especially anaerobic infection, and fungal infections including histoplasmosis, coccidioidomycosis, and blastomycosis. Lung carcinoma can mimic tuberculosis and the two diseases can coexist. Surgery is frequently necessary for a definitive diagnosis, expecially when the disease is seen as a noncalcified nodule.

Adult↗

Infectious mononucleosis complicated by severe Mycoplasma pneumoniae infection.

A 14-year-old girl with infectious mononucleosis and secondary immunosuppression had severe dyspnea and cough, spiking fever, rales, and diffuse bilateral pulmonary infiltrates. The pulmonary disease progressed rapidly, necessitating empiric trials of antimicrobial agents. Mycoplasma pneumoniae was isolated from a lung biopsy specimen, transtracheal aspirate, and expectorated sputum, but the relatively long period required to isolate the organism delayed the microbiologic diagnosis. Serologic study of acute and convalescent serum samples confirmed the M pneumoniae infection. Clinical improvement was gradual, and the immunosuppression was transient. The patient's illness appeared to represent microbial synergism, with severe M pneumoniae infection complicating transient immunosuppression induced by infectious mononucleosis.

Adolescent↗

Cast bronchitis in infants and children.

Seventy-two children (age range, 3 months to 5.5 years) with a clinical diagnosis of obstructive bronchitis (asthmatoid or spastic bronchitis or bronchiolitis) were found to have bronchial casts in the gastric fluid, and in 2 additional cases casts were spontaneously expectorated in the bronchial exudate. Cast bronchitis had a long-term course of 10 to 24 months in 65 of the 74 patients. Common radiologic findings included bronchi presumably filled with secretions, areas of atelectasis, and lung emphysema of varying degrees. Cast bronchitis did not appear to be associated with eosinophilia and elevated serum IgE levels. Therefore, an extrinsic allergic mechanism is not likely involved in the pathogenesis of the condition. Bronchial casts had varying consistencies; although they were usually soft, they were sometimes rather hard. They were hollow, often ramified, and white and measured from 0.5 to 2 cm in length. Histologically, they consisted of metaplastic squamous epithelium with a varying degree of inflammatory cells and noncellular material. Some differences in biochemical composition were observed between bronchial casts and bronchial exudate of acute catarrhal bronchitis. No viruses could be isolated in 11 cast specimens. Our results suggest that cast formation is mainly related to the metaplastic transformation of the bronchial epithelium and that this metaplasia may play an important pathophysiologic role in certain infants and children with obstructive bronchitis.

Bronchi↗

Chronic pancreaticopleural fistulas.

We report two cases of chronic pancreaticopleural fistulas occurring in chronic pancreatitis. In both cases the primary clinical manifestation was a recurrent left pleural effusion with a high content of pancreatic amylase. The pleural effusion was associated with subcutaneous fat necrotic lesions in one patient, and with expectoration of an amylase-rich fluid in the other. Endoscopic retrograde cholangiopancreatography is important because this examination allows a precise evaluation of the ductal morphology and is indispensable to the surgical procedure. We recommend surgical treatment when the fistula does not close spontaneously within two weeks. Both patients were successfully treated by surgery.

Aged↗

Respiratory therapy. Current practice in ambulatory patients with chronic airflow obstruction.

The role of respiratory therapy in treating ambulatory patients with chronic obstructive pulmonary disease is becoming more clearly defined. Oxygen therapy on a continuous basis is needed for patients with arterial PO2 values below 45 mm Hg and should be considered for patients with arterial PO2 values between 45 and 55 mm Hg who have chronic cor pulmonale, erythrocytosis with hematocrit value greater than 55%, and disturbances of cognition and sleep. Concentrated bronchodilator and corticosteroid aerosols have established roles in therapy; the place of bland aerosols is less clear They may increase ease of expectoration and should be given by simple compressed-air nebulizer systems; their administration by brief periods of intermittent positive-pressure breathing is rarely justified. Three-positional, postural drainage with chest percussion and vibration may be helpful in mobilizing secretions in patients with severe disease.

Aerosols↗

Estrogen-induced microvilli and microvillar channels and entrapment of surfactant-lipids by alveolar type I cells of bovine lung.

The ATI cells are simple, flat squamous epithelial cells, which are evolved to function as a component of the alveolar-capillary membrane, ideally designed for gaseous exchange. They inherently lack an active metabolic machinery and lead a precarious existence in the face of hostile environment. On the other hand, the ATI cells of the lung of ruminating animals are endowed with structure-functional properties which enable them to exert a selective barrier function against a wide range of osmotic pressure gradients at their luminal surface. Such gradients are created by a complex gaseous homeostasis due to expectoration of several gases and volatile fatty acids originating from the complex stomach of the ruminants. The purpose of this study is to examine the effect of estradiol propionate on the ultrastructure of the ATI cells and their interaction with the surfactant lipids. The lungs of estrogen and dexamethasone treated male calves were harvested for electromicroscopic examination. The evidence is presented that estradiol induced the formation of microvilli and microvillar channels at the luminal surface. At these regional modifications, intense interactions with the surfactant lipids and their entrapment into the pathways of endocytosis, took place in the squamous part of the ATI cells. Concurrently, large basal protrusions ended up as long lamellipods deep into the alveolar interstitium. The filamentous cytoskeletal network and microtubules intermixed with the translocated organelles such as Golgi apparatus and associated coated and uncoated vesicles. The results of this study support the hypothesis that estrogen regulate the selective barrier-function of the ATI cells. The entrapment of surfactant lipids under the influence of estrogen by ATI cells is a significant change perhaps in response to extracellular stimuli and expression of transmembrane receptors. It implies that these epithelial cells are specially evolved to adapt to a complex gaseous homeostasis in the lung of the ruminating ungulates.

Animals↗

Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis.

Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick secretions, which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline (HS) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions, and may therefore provide a low cost alternative. We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease. The patients were evaluated following 2 weeks of treatment with HS in an open-label study. Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6% NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of salbutamol was administered prior to the nebulized solutions. A symptom score was recorded and spirometry was performed on day 0 before therapy was started, on day 14 (the last day of therapy), and on day 28 (14 days after the last treatment with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2 (range 7-36) years completed the study. There was no difference in baseline characteristics between the two groups. Following 2 weeks of treatment, there was a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD) in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS therapy (P = 0.004). Furthermore, there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS (P = 0.02). The treatment was well tolerated. We conclude that in patients with CF, ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period. Nebulized saline also enhances the perception of effectiveness of chest physiotherapy.

Administration, Inhalation↗

Persistent pulmonary consolidation treated with intrapulmonary percussive ventilation: a preliminary report.

Intrapulmonary percussive ventilation (IPV) is a novel form of chest physiotherapy delivered by a percussive pneumatic device (IPV, Percussionaire, Sand Point, ID). There are few published reports about the use of IPV for diseases other than cystic fibrosis. We report our experience with three pediatric patients and one adult patient with persistent pulmonary consolidation refractory to conventional therapies. Three of the four patients had neuromuscular disease; one patient had segmental atelectasis due to aspiration. Three of the four patients showed clinical and radiographic improvement within 48 hours of starting IPV. The fourth patient experienced brief episodes of third-degree atrioventricular block, hypoxemia, and bradycardia during two IPV treatments. IPV was safely restarted and he slowly improved. We conclude that while IPV requires further clinical evaluation, it appears to be a safe and effective therapy for selected patients. However, close observation is essential during and after IPV treatments, especially in patients who have difficulty mobilizing or expectorating sputum.

Adolescent↗

Pattern of airway inflammation and its determinants in children with acute severe asthma.

The aim of this study was to examine the relationship between sputum cell counts and clinical variables in children with an acute exacerbation of asthma. Sputum was successfully obtained from 37 of 42 children presenting to the Emergency Department with acute asthma, using ultrasonically nebulized normal saline (n = 19) or spontaneous expectoration (n = 18). Sputum portions were selected and dispersed, and total and differential cell counts were performed. Sputum supernatant was assessed for eosinophil cationic protein (ECP), interleukin (IL)-5, and IL-8. The exacerbations were of 3 inflammatory cell patterns: eosinophilic (n = 16 or 43% of total), combined eosinophilic/neutrophilic (E/N; n = 13.3 or 35% of total), or noneosinophilic (n = 8 or 22% of total). IL-5 was highest in eosinophilic exacerbations. Combined E/N exacerbations had increased mast cells (77%) and higher sputum ECP levels than eosinophilic exacerbations: 2,146 ng/mL vs. 666 ng/mL (P = 0.04). The speed of onset of the exacerbation was not related to the inflammatory cell profile. Logistic regression identified maintenance asthma treatment (odds ratio (OR), 5.9; 95% confidence interval (CI), 1.3-26.8) and lung function during the acute episode (OR, 4.0; 95% CI, 1.7-93) as significantly associated with the intensity of sputum eosinophilia. Eosinophils were lowest in children who received maintenance treatment with oral corticosteroids compared to those with no background asthma preventer therapy (P = 0.001). In conclusion, we identified three distinct patterns of airway inflammation in children with acute asthma; they included increased eosinophils, combined eosinophilic-neutrophilic infiltration, and a noneosinophilic pattern. Eosinophil degranulation was greatest with the combined eosinophilic/neutrophilic pattern of airway inflammation. Sputum eosinophils were associated with clinical severity, and background asthma therapy, but not with outcome, nor with speed of onset of exacerbations. These different inflammatory cell profiles imply different etiological agents and may require differing treatment strategies.

Acute Disease↗

Bronchial casts in children with cardiopathies: the role of pulmonary lymphatic abnormalities.

Expectoration of bronchial casts, a condition also called plastic bronchitis, is very rare in children. Bronchial casts may be associated with bronchopulmonary diseases associated with mucus hypersecretion, bronchopulmonary bacterial infections, congenital and acquired cardiopathies, or pulmonary lymphatic abnormalities. A classification based on anatomy and pathology has been proposed which identifies an "acellular" group associated with congenital cardiopathies and palliative surgery. We report on 3 cases with bronchial casts associated with cardiopathy. Observations suggest that the formation of bronchial casts may result from lymphatic leakage into the bronchi. The 3 cases on which we report were immunodeficient and had pulmonary lymphatic abnormalities. The bronchial casts contained lymphocytes and lipids, as determined by histologic examination. In the absence of congenital pulmonary or diffuse lymphatic dysplasia associated with cardiopathy, the principal factors resulting in the formation of bronchial casts appear to be surgical trauma to the lymphatic channels surrounding the bronchi, pleural adhesions, and high systemic venous blood pressure. The prognosis for these patients is poor, and possibilities for treatment are limited.

Bronchial Diseases↗