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PubMed2001

Chronic obstructive pulmonary disease: an overview of pathology and pathogenesis.

A cigarette smoke-induced inflammatory process underlies the pathogenesis of the majority of pathologic lesions associated with chronic obstructive pulmonary disease (COPD). In chronic bronchitis, this process is located in the mucosa, gland ducts and glands of intermediate sized bronchi with an internal diameter of 2-4 mm. The mucus-containing exudate produced by the inflammatory response overpowers the normal clearance mechanisms, resulting in the cough and expectoration that characterize chronic bronchitis. In some cases of chronic bronchitis, the inflammatory process extends to smaller bronchi and bronchioles less than 2 mm in internal diameter. In this location, the inflammatory process thickens the wall, narrows the lumen and destroys the parenchymal support of the airways. These changes progressively increase peripheral airways resistance and eventually reduce the patient's ability to empty their lungs to a degree that can be measured by a reduction in FEV1 (forced expiratory volume in one second). The reduction in lung surface area produced by parenchymal inflammation contributes to the decline in FEV1 by reducing lung elastic recoil, which is the major force driving air out of the lung. It also contributes to the reduction in diffusing capacity by reducing the lung capillary bed. The purpose of this presentation is to review the quantitative aspects of these pathological changes and attempt to provide insight into factors which result in progression of these lesions.

Animals↗
PubMed1980

Asbestosis in the industries of the Barcelona area.

This presentation is the result of the survey of eight industries with asbestosis risk in the Barcelona area (two of fibro-cement, three of auto brakes, two of textiles, and one of insulation materials). Of 1,472 workers, 271 or 18.5% have asbestosis. Pleural involvement in asbestosis is twice as common as that of the lung, 15.7% versus 8.5%. Pulmonary asbestosis without pleural participation is seen in only 2.6% of cases. Pleural plaques, calcified and not calcified, are detected in only a few cases. There is a definite correlation between the incidence of asbestosis and the exposure time: from 1% in the group of workers with less than five years of exposure up to 64.58% for those with 30 or more years of exposure. Clinical symptoms (cough, and/or expectoration, and/or dyspnea) were present in 68% of the studied population. Pulmonary crepitations are the most significant physical sign detected, observed in one quarter to one third of the patients. Pulmonary function tests in asbestos workers revealed restrictive and mixed type syndromes in 17% of the cases and obstructive syndrome in 36%. The percentages for those workers without asbestosis are 9% and 16%, respectively. It seems, therefore, that a bronchial factor plays a role in asbestosis. The bronchial pathology would be manifested clinically by the appearance or the exaggeration of the chronic bronchitis symptoms, and physiologically by the presence of the obstructive syndrome. There is no doubt that smoking enhances the incidence of asbestosis, aggravates the respiratory symptoms in those affected, and is a cause of further deterioration of pulmonary function.

Adolescent↗
PubMed1988

Pulmonary complications after subtotal oesophagectomy.

The postoperative pulmonary complications in 25 patients undergoing subtotal oesophagectomy for intrathoracic oesophageal carcinoma during the 3-year period 1981-1983 were compared with those of 25 patients undergoing surgery from 1984 to 1986. Although more extensive lymphadenectomies were performed from 1984, the mortality rate caused by the postoperative pulmonary complications was zero in the later period (1984-1986) compared with a rate of 16 per cent in the earlier period (1981-1983). The incidence of postoperative pulmonary complications was lower in the later series but the difference was not statistically significant. Factors which may have contributed to the decrease in critical pulmonary complications after surgery during the later period were the selection of the posterior mediastinal route for reconstruction, the introduction of selective endobronchial intubation by a double lumen tube with combined epidural anaesthesia, fluid restriction during and after surgery, postoperative mobilization and the administration of an expectorant.

Aged↗
PubMedDate not supplied

Community-acquired bacterial pneumonia in the elderly.

Pneumonia remains the leading infectious disease-related cause of death among the elderly. Streptococcus pneumoniae is the most frequent pathogen isolated from aged individuals with community-acquired pneumonia. Other common bacteria that cause this disease include Haemophilus influenzae and Legionella pneumophila. Manifestations of pneumonia in the elderly can be subtle and result in delayed recognition and treatment. Gram stain evaluation and culture of non-contaminated expectorated sputum remain the conventional techniques to guide initial antibiotic selection. While the presence of a new infiltrate on chest X-ray confirms the clinical diagnosis of pneumonia, the radiographic appearance of the infiltrate cannot accurately define the etiologic agent. Specific therapeutic measures include administration of appropriate antibiotics, correction of fluid and electrolyte imbalances, nutritional support and treatment of concomitant disorders. Preventive measures include use of influenza vaccine, amantadine and pneumococcal vaccine.

Aged↗
PubMed1983

Mutagenic effects of aqueous extracts of Symphytum officinale L. and of its alkaloidal fractions.

Symphytum officinale L. (Boraginaceae) is a medicinal plant widely used in therapy. It roots, described in the Polish Pharmacopoeia as Radix symphyti, are recommended as expectorants, especially for children. Aqueous solutions of three alkaloid fractions obtained from infusions of Symphytum officinale L. root were tested for their antimitotic and mutagenic activity in meristematic cells of the lateral roots of Vicia faba L., var minor. Lasiocarpine, a proven carcinogen, served as a positive control. Mutagenic effects were induced by lasiocarpine, by the alkaloidal fraction I and by diluted infusions from Radix symphyti. Fraction III had only antimitotic effect. The biological activity of the tested solutions is discussed in relation to the relevant literature.

Alkaloids↗
PubMed1990

An epidemic of respiratory syncytial virus in elderly people: clinical and serological findings.

In 1984-1985, an outbreak of respiratory syncytial virus (RSV) infection occurred in two geriatric wards. Among 68 patients (mean age +/- SD = 82.5 +/- 12.5 with respiratory signs, 52 had signs caused by RSV infection. Among all patients, the clinical and serological attack rates were 61.2% and 75.0%, respectively. The most frequent clinical presentation was intensive coughing (96.1%) and fever (96.1%) associated with expectorate (63.5%). The duration of the respiratory symptoms was 5 to 7 days. The disease gradually resolved, although in eight (15.4%) patients complications occurred. For periods of up to 1 year after infection, 172 sera were obtained and tested by complement fixation test (CFT), fluorescent assays for titrating specific IgG, IgA, and IgM, and Western blotting. Specific IgM appeared in six (11.5%) of the infected patients and peaked 2 to 6 months after infection, and there was no significant correlation with severity of clinical symptoms. However, higher peak G and A antibody responses were observed in persons with rales (CFT: P = 0.008; IgG: P = 0.042; IgA: P = 0.020), cough (IgG: P = 0.034), sputum (IgG: P = 0.030), dyspnea (CFT: P = 0.024), conjunctivitis (CFT: P = 0.025), and bronchitis (CFT: P = 0.018). The temporal patterns of IgA and CFT results were found to be similar, whereas IgG peaked later, i.e., between 2 and 6 months. The patients with the most severe symptoms had the highest antibody titers obtained by conventional tests and by Western blots. Thus, RSV can be an epidemic pathogen among elderly persons, although this illness is usually mild.

Aged↗
PubMed2003

Treatment of cast bronchitis with low-dose oral azithromycin.

Cast or plastic bronchitis is an unusual disorder that is rarely encountered in the pediatric population. It is characterized by the expectoration of large, branching plugs of airway debris. These "casts" conform to the shape of portions of the tracheobronchial tree, and give the disorder its name. Cast bronchitis is typically seen in association with several primary pulmonary disorders and cyanotic congenital heart disease. It can be classified as inflammatory or acellular, based on the histologic characteristics of the casts. The presence of large, obstructive plugs filling the airways of lobes or entire lungs can result in a variety of clinical signs and symptoms, and may ultimately lead to respiratory failure and death. Conventional treatment of cast bronchitis has focused on the clearance of obstructing material from the airways combined with therapy for any underlying cardiopulmonary disease. Unfortunately, this approach has not proven very effective, and patient mortality remains high. We report on a case in which a patient with cast bronchitis was treated with long-term, low-dose oral azithromycin. This therapy resulted in clinical, spirometric, and radiographic improvement of the patient.

Adolescent↗
PubMed2003

The "wandering needle".

Suspected aspiration of a radiopaque foreign body can easily be confirmed by a chest film. We report a case of a boy with chest-film confirmed aspiration of a needle into his right main bronchus, in whom no needle was found during bronchoscopy. In retrospect, the boy had expectorated the needle without noticing it in the interval between making the diagnosis and the actual bronchoscopy. We propose to reconfirm aspiration of a radiopaque foreign body by fluoroscopy shortly before commencing bronchoscopy.

Bronchi↗
PubMed1995

Bronchial artery embolization in the management of hemoptysis in cystic fibrosis.

Massive hemoptysis and/or recurrent expectoration of measurable amounts of blood are common complications of chronic bronchopulmonary infections in cystic fibrosis (CF). When conservative treatment fails to control bleeding, surgery or bronchial artery embolization (BAE) is frequently considered. We present our experience and long-term follow up of BAE in 14 CF patients (age range 15-39 years) with massive (6 subjects) and/or recurrent (8 subjects) hemoptysis not responsive to medical treatment. Seven had chronic hypercapnic respiratory failure. After angiographic evaluation, polyvinyl alcohol particles (Ivalon) were injected to embolize obviously enlarged bronchial arteries. Seventeen procedures were performed in 14 patients and 36 bronchial arteries were embolized. All the patients stopped bleeding immediately upon BAE. Most of the patients had postembolization fever, dysphagia, and transient chest pain which were managed symptomatically. After a median follow-up period of 10.5 months (range 0.5-38 months), no recurrence of hemoptysis was observed in 8 patients who are still alive. In 3 patients hemoptysis recurred and they underwent reembolization after 3, 22, and 25 months, respectively. Three subjects died of respiratory failure within 5 months from BAE. Presently, 50% of patients studied had a > or = 1 year interval free of major hemoptysis after the first BAE. Our experience indicates that massive and/or recurrent hemoptysis in CF patients can be safety and effectively managed by BAE if the procedure is performed by a skilled practitioner. The procedure was well tolerated and resulted in prolonged and satisfactory bleeding control in most patients.

Adolescent↗
PubMed2004

Effect of DNase on exercise capacity in cystic fibrosis.

DNase can reduce viscosity and facilitate expectoration of airway secretions in cystic fibrosis (CF) lung disease. We evaluated its effect on exercise performance in relation to resting pulmonary function. Fifteen sputum-producing CF patients (aged 9-28 years; FEV1 22-83% predicted) performed spirometry, body plethysmography, nitrogen washout, and incremental cardiopulmonary exercise testing before and after 8 weeks of first-time treatment with daily inhaled rhDNase. Most subjects reported increased amounts and fluidity of sputum. The effect on objective parameters was heterogeneous, without statistical significance. Groupwise, FEV1 increased by 6% without correlation to baseline values; individual patients gained up to 40%. Indices of hyperinflation and air trapping were slightly raised. Maximal workload and oxygen uptake (V'O2) increased by up to 20% in a number of patients. The treatment effect on V'O2 was neither related to baseline levels of pulmonary function and exercise capacity nor to the change in FEV1. Ventilatory equivalents for oxygen and carbon dioxide during exercise were slightly but insignificantly lower after DNase treatment; minimal O2 saturation was unaffected. We conclude that improvement of exercise performance with DNase is restricted to a subgroup of CF patients and may not be predicted or identified by spirometry and subject report alone.

Administration, Inhalation↗
PubMed2004

Effects of betaine, coumarin and flavonoids on mucin release from cultured hamster tracheal surface epithelial cells.

Betaine, coumarin, hesperidin and kaempferol are the components derived from Lycium chinense, Angelicae decursiva, Poncirus trifoliata and Polygonatum odoratum, respectively. These plants have been used for the treatment of respiratory diseases in oriental medicine and their respective components were reported to have various biological effects. In this study, we investigated whether these natural products affect mucin release from cultured hamster tracheal surface epithelial cells and compared the possible activities of these agents with the inhibitory action on mucin release by poly-L-lysine and the stimulatory action by adenosine triphosphate. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled using (3)H-glucosamine for 24 h and treated for 30 min in the presence of varying concentrations of each agent to assess the effects on (3)H-mucin release. The results were as follows: (i) Coumarin and kaempferol did not affect mucin release significantly; (ii) Betaine and hesperidin increased mucin release at the highest concentration; (iii) Poly-L-lysine inhibited and adenosine triphosphate increased mucin release. We conclude that betaine and hesperidin can increase mucin release by direct acting on airway mucin-secreting cells and suggest these agents be further studied for the possible use as mild expectorants during the treatment of chronic airway diseases.

Animals↗
PubMed1993

Direct monitoring as well as sensitive diagnosis of Pneumocystis carinii pneumonia by the polymerase chain reaction on sputum samples.

In order to evaluate the usefulness of the polymerase chain reaction (PCR) for diagnosis and monitoring of Pneumocystis carinii pneumonia (PCP) in specimens obtained from non-invasive techniques, expectorated or induced sputa were collected from 30 patients who were tentatively diagnosed as having PCP and administered intravenous trimethoprim-sulfamethoxazole. Using appropriate criteria, 13 of these cases were diagnosed as having PCP, 12 cases were diagnosed of other pulmonary diseases, and five cases were omitted from the study according to the exclusion criteria. PCR was performed using primers based on the P. carinii 5S rRNA sequence. Pneumocystis carinii was detected in nine of the 13 defined cases (sensitivity of 69%) and in none of 12 non-PCP cases (specificity of 100%). In contrast, P. carinii was detected in only one case by microscopic examination using Diff-Quik stain. Therefore, the sensitivity of PCR was significantly higher than that observed with the stain (P < 0.05, chi 2 = 6.125). Sputum samples were also obtained from eight cases during the treatment. The eradication of P. carinii from the sputum as judged by PCR varied from three to 38 days (median 6.5 days) after the start of the treatment. Pneumocystis carinii shedding in sputum correlated with the time between initial clinical symptoms and initiation of the treatment (P < 0.05, r = 0.810), but not with the tension of PaO2 at the time of diagnosis. This preliminary study demonstrates that PCR allows early diagnosis of PCR and that close monitoring with non-invasive specimens can be performed by PCR.

Adrenal Cortex Hormones↗
PubMed1994

Addition of a bacterial alginate lyase to purulent CF sputum in vitro can result in the disruption of alginate and modification of sputum viscoelasticity.

Alginate is a large molecular weight exopolysaccharide present in the purulent airway secretions of cystic fibrosis (CF) patients. This polymer, produced by some of the opportunistic pathogens associated with the recurrent lung infections characteristic of CF, has been suggested to effect an increase in the viscoelastic properties of purulent CF airway secretions. We have investigated the use of an enzyme targeted at this exopolysaccharide, an alginate lyase obtained from a bacterial source, to disrupt its polymeric nature and effect a change in the rheological properties of CF sputum in vitro. Expectorated sputum samples obtained from hospitalized CF patients were found to contain 80-200 micrograms alginate per ml sputum with no measurable endogenous alginate lyase activity. Treatment with exogenous alginate lyase prepared from a mucoid strain of Pseudomonas aeruginosa resulted in the disruption of alginate and a decrease in sputum viscoelasticity in a small percentage of the samples tested. Similar treatment of these samples with recombinant human deoxyribonuclease I to cleave DNA present in purulent sputum and the use of alginate extracted from sputum as an alginate lyase assay substrate suggested that the inability of the exogenous alginate lyase to disrupt sputum alginate was not due to substrate inaccessibility or an unresponsive substrate. Concentrations of Ca2+ and Zn2+ in alginate lyase-resistant sputum samples, determined by metal ion analysis, were found to inhibit enzyme activity in studies using seaweed alginate as a substrate. High concentrations of Ca2+ and Zn2+ in sputum samples initially resistant to lyase activity could be reduced significantly in some samples by dialysis and these same samples acquired sensitivity to the lyase. Other sputum samples did not show reduced concentrations of Ca2+ and Zn2+ following dialysis and these samples remained lyase-insensitive. Together, these results suggest that bacterial alginate present within purulent CF sputum may be quite stable, that endogenous alginate lyase activities appear to be limited and that the in vitro addition of exogenous alginate lyase can lead to the disruption of alginate and a change in the viscoelastic properties of some purulent CF sputum samples.

Alginates↗
PubMedDate not supplied

Methods of recording and analysing cough sounds.

Efforts have been directed to evolve a computerized system for acquisition and multi-dimensional analysis of the cough sound. The system consists of a PC-AT486 computer with an ADC board having 12 bit resolution. The audio cough sound is acquired using a sensitive miniature microphone at a sampling rate of 8 kHz in the computer and simultaneously recorded in real time using a digital audio tape recorder which also serves as a back up. Analysis of the cough sound is done in time and frequency domains using the digitized data which provide numerical values for key parameters like cough counts, bouts, their intensity and latency. In addition, the duration of each event and cough patterns provide a unique tool which allows objective evaluation of antitussive and expectorant drugs. Both on-line and off-line checks ensure error-free performance over long periods of time. The entire system has been evaluated for sensitivity, accuracy, precision and reliability. Successful use of this system in clinical studies has established what perhaps is the first integrated approach for the objective evaluation of cough.

Computers↗
PubMed2002

Herbal antitussives.

The mechanisms of actions of cough medicines are not always known. The problem is exacerbated for herbal medicines, where the effectiveness of the plant or its phytochemicals have rarely been carefully evaluated. Moreover, the most active phytomedicinal constituent is difficult to identify, and the expense and difficulty of such studies discourages sponsors who may not be able to benefit by subsequent exclusive marketing of the herbal remedy. Most popular herbs used as cough medicines appear to be demulcents whose action is confined to the oropharynx. It is probable that the vast majority of allegedly effective herbal cough medicines act as non-specific emetic-expectorants. The proof of activity of even marketed herbal derivatives such as guaifenesin and codeine is difficult to obtain. It is therefore likely that herbal cough medications will never be shown to be more active than placebos. Nevertheless, these plant products will continue to be popular remedies for patients and their health care advisors.

Antitussive Agents↗
PubMed1984

Interaction of granulocyte proteases with inhibitors in pulmonary diseases.

The elastase-antielastase hypothesis of lung tissue destruction has focused our interest on the two main inhibitors of granulocyte elastase in the lung, alpha 1-antitrypsin dominating blood, interstitial tissue and alveolar fluid lining and antileukoprotease dominating the respiratory tract mucosa. Antileukoprotease as well as elastase and alpha 1-antitrypsin show increased serum levels during bronchitis and bronchopneumonia, alpha 1-antitrypsin because it is an acute phase reactant, elastase and antileukoprotease because of influx from the inflamed tissues. Elastase is identified in the bronchial expectorates, mainly in complex with antileukoprotease, but often also in a free, active form. The granulocyte elastase in serum from these patients is, however, only found in complex with alpha 1-antitrypsin. The increased amounts of antileukoprotease in serum are always in a free and largely active form. The explanation for the absence of elastase-antileukoprotease complexes in serum is offered by some of our recent results. The elastase-antileukoprotease complexes are rapidly dissociated when mixed with serum in vitro, although the equilibrium dissociation constant Ki of the complex is 1.2 X 10(-11) M. Furthermore, in a pure in vitro system, alpha 1-antitrypsin is able to dissociate a leukocyte elastase-antileukoprotease complex with the rate constant of 1.3 X 10(-4) X S-1. A small part of the antileukoprotease released from the elastase-antileukoprotease complex on mixture with serum is recovered bound by elastase-alpha 2-macroglobulin complexes. Antileukoprotease inhibits the enzymatic activity of elastase-alpha 2-macroglobulin complex relatively slowly. 1:1 elastase-alpha 2-macroglobulin complexes are, however, inhibited more readily than 2:1 saturated complexes.

Bronchitis↗
PubMed1988

Respiratory function in flour-mill workers.

The frequency of bronchial symptoms and the alteration of respiratory function parameters were studied in a group of 63 workers of an industrial flour-mill, and in a control group matched according to age, social class, and tobacco intake. In the exposed group the answers to a questionnaire indicated a greater incidence of cough (p less than 0.01) and chronic expectoration (p less than 0.01) as well as clinical airway hyperreactivity (p less than 0.01). No differences were noted for either asthma or allergy. The respiratory function parameters did not differ between the two groups studied. These results suggest that workers exposed to the vegetable dust found in fluor-mills are subject to develop chronic bronchial irritation.

Adult↗
PubMed1988

Salivary concentrations of hexamethylene bisacetamide (HMBA) in patients receiving 5-day continuous infusions.

Salivary and plasma concentrations of hexamethylene bisacetamide (HMBA) were studied to determine (1) how the concentrations of HMBA achieved in saliva compared with those required to induce differentiation in vitro, and (2) whether saliva might substitute for plasma as a biologic fluid on which to base dosage adjustment. Plasma and expectorated saliva were collected concomitantly from 16 patients receiving 5-day continuous infusions of HMBA. The concentrations of HMBA in each fluid were determined by gas chromatography. The patients displayed a range of periodontal disease from gingivitis to complete edentia, but periodontal disease status did not appear to influence the salivary behavior of HMBA, which mirrored that of the drug in plasma, with concentrations of HMBA increasing in both fluids during the first 12-16 h of infusion. Between 24 and 120 h, HMBA concentrations in saliva and plasma remained constant. In some patients, salivary HMBA concentrations lagged behind those in plasma during the first 6-8 h of infusion, but after that the salivary HMBA concentrations approximated those in the plasma. Salivary concentrations of HMBA between 0.96 and 2.56 mM were associated with nontoxic plasma concentrations of HMBA. Therefore, in patients with restricted venous access, saliva might be a suitable substitute for plasma if adaptive control-dosing schemes for HMBA are employed. Moreover, the concentrations of HMBA in saliva bathing the oral cavity are quantitatively comparable to those required for induction of cell differentiation in vitro.

Acetamides↗