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A patient who has expectorated bronchial casts for 23 years is reported. The casts contained mucus, fibrin, and lymphocytes, and the resected middle lobe showed dilated lymphatics with thickened walls at the hilum and lymphoid aggregates in the terminal bronchioles.
BACKGROUND: Airway inflammation is considered to be important in asthma but is relatively inaccessible to study. Less invasive methods of obtaining sputum from patients unable to produce it spontaneously should provide a useful investigational tool in asthma. METHODS: A method to induce sputum with inhaled hypertonic saline was modified for use in 17 asthmatic patients and 17 normal subjects who could not produce sputum spontaneously. The success rate and safety of the method, the reproducibility of cell counts, and differences in cell counts between the asthmatic and normal groups were examined. Hypertonic saline solution 3-5% was inhaled for up to 30 minutes after inhalation of salbutamol. Subjects were asked to expectorate sputum every five minutes. The quality of the sample was scored on the volume of plugs and the extent of salivary contamination. Plugs from the lower respiratory tract were selected for a total cell count and for differential cell counts of eosinophils and metachromatic cells (mast cells and basophils) in direct smears. RESULTS: Adequate samples from the lower respiratory tract were obtained in 76% of first attempts. The mean fall in the forced expiratory volume in one second (FEV1) during inhalation of saline was 5.3% and the maximum fall 20%. Eosinophil and metachromatic cell counts were reproducible (reliability coefficient 0.8 and 0.7 respectively). When compared with sputum from normal subjects sputum from asthmatic patients contained a significantly higher proportion of eosinophils (mean 18.5% (SE 3.8%) v 1.9% (0.6%)) and metachromatic cells (0.50% (0.18%) v 0.039% (0.014%)). In the asthmatic group the differential eosinophil count correlated with the baseline FEV1. CONCLUSION: Induced sputum is capable of detecting differences in cell counts between normal and asthmatic subjects and merits further development as a potential means of assessing airway inflammation in asthma.
BACKGROUND: Anticholinergic bronchodilator drugs improve lung function in chronic bronchitis but less is known of their effects on the volume and physical properties of sputum in conditions associated with excessive airway secretions. This study examines the effects of the regular use of oxitropium bromide in such patients. METHODS: The study was conducted in a parallel, double blind, placebo controlled fashion. Patients were divided into two groups: the first group (n = 17) received oxitropium bromide from a metered dose inhaler (two puffs three times daily; 100 micrograms/puff) for eight weeks, and the second group (n = 16) received placebo. Lung function was measured as forced expiratory volume in one second (FEV1) and vital capacity. In evaluating airway secretion, daily amount of expectorated sputum, percentage solid composition, viscoelastic properties including elastic modulus and dynamic viscosity, and sputum microbiology were determined. RESULTS: Oxitropium bromide increased FEV1 and decreased the mean (SE) sputum production from 61(4) to 42(3) g/day after treatment, whereas placebo had no effect. Bacterial density and sputum flora were unchanged, but solid composition and elastic modulus increased from 2.52(0.43)% to 3.12(0.34)%, and 68(12) dyne/cm2, respectively, in the group taking oxitropium bromide. CONCLUSIONS: Regular treatment with oxitropium bromide not only improves airflow limitation but also reduces sputum production, probably through the inhibition of both mucus secretion and water transport, the latter component being predominant.
BACKGROUND: In vitro studies have suggested that both the viscoelastic properties of lung secretions and the peak flow attained during simulated cough influence clearance. This study examines the possible association of the viscoelastic properties of sputum and maximum expiratory flow with measured effectiveness of mucus clearance induced by instructed cough and by forced expiration technique (FET) in patients with airways obstruction. METHODS: Nineteen patients (11 men and eight women) of mean (SE) age, % predicted FEV1, and daily sputum wet weight of 64 (2) years, 52 (6)%, and 37.5 (7.9) g respectively participated in the study. Mucus movement from proximal and peripheral lung regions was measured by an objective non-invasive radioaerosol technique. Each patient underwent three assessments: control, cough, and FET. During cough and FET, maximum expiratory flow was measured at the mouth level. Apparent viscosity and elasticity of the expectorated sputum samples were measured with a viscometer. RESULTS: Compared with the control run (mean (SE) clearance: 16 (3)%) there was an increase in clearance from the whole lung during cough (44 (5)%) and FET (42 (5)%), and also an enhanced clearance of inhaled, deposited radioaerosol from the trachea, inner and intermediate regions of the lungs, but not from the outer region. There were, however, no differences in regional clearance between cough and FET. Neither regional nor total clearance correlated with maximum expiratory flow, apparent viscosity, elasticity, or daily sputum wet weight. CONCLUSIONS: These results confirm that cough and FET both promote effective clearance but suggest that, unlike in vitro studies, sputum production and viscoelasticity, as well as maximum expiratory flow, provide no guide to clearance efficacy in humans.
BACKGROUND: The importance of cytokines in the asthmatic inflammatory response is becoming apparent. The aim of this study was to determine whether the non-invasive method of induced sputum combined with the polymerase chain reaction would allow the detection of messenger RNA (mRNA) encoding a range of cytokines on a qualitative basis. METHODS: Four groups were studied comprising 10 normal subjects, six atopic, 10 mild and five moderately severe asthmatic subjects. Sputum was induced by the inhalation of nebulised 3.5% saline and total RNA extracted from the expectorated cells. Expression of cytokine message within induced sputum was examined by reverse transcription and the polymerase chain reaction (PCR) using primers specific for a range of cytokines (IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, RANTES, TNF alpha, IFN alpha, IFN gamma). Presence or absence of the signal was determined at 35 and 70 cycles of PCR by electrophoretic size fractionation on ethidium bromide stained agarose gels. RESULTS: Cytokine message was detectable in sputum by this method. All samples showed a positive result for actin control. Analysis of signal for the cytokines in all subjects showed that, at 70 cycles, IL-1, IL-5, IL-8, and TNF alpha were detected in more subjects than would be expected by chance. IL-5 mRNA was detected in more of the asthmatic patients (moderate 80%, mild 40%) than in the atopic subjects (33%), who in turn showed expression of this cytokine in more individuals than nonatopic subjects (10%). CONCLUSIONS: The combination of sputum induction and PCR appears to be a useful, non-invasive tool to explore the chronic inflammation of asthma and possibly other lung disorders. It should enable differences between normal and asthmatic subjects to be identified for future confirmation by quantitative techniques.
BACKGROUND--Autogenic drainage has been suggested as an alternative method of chest physiotherapy in patients with cystic fibrosis. In this study autogenic drainage was compared with the active cycle of breathing techniques (ACBT) together with postural drainage. METHODS--Eighteen patients with cystic fibrosis took part in a randomised two-day crossover trial. There were two sessions of one method of physiotherapy on each day, either autogenic drainage or ACBT. The study days were one week apart. On each day the patients were monitored for six hours. Mucus movement was quantified by a radioaerosol technique. Airway clearance was studied qualitatively using xenon-133 scintigraphic studies at the start and end of each day. Expectorated sputum was collected during and for one hour after each session of physiotherapy. Pulmonary functions tests were performed before and after each session. Oxygen saturation (SaO2) and heart rate were measured before, during, and after each session. RESULTS--Autogenic drainage cleared mucus from the lungs faster than ACBT over the whole day. Both methods improved ventilation, as assessed by the xenon-133 ventilation studies. No overall differences were found in the pulmonary function test results, but more patients had an improved forced expiratory flow from 25% to 75% with autogenic drainage, while more showed an improved forced vital capacity with ACBT. No differences were found in sputum weight and heart rate, nor in mean SaO2 over the series, but four patients desaturated during ACBT. CONCLUSIONS--Autogenic drainage was found to be as good as ACBT at clearing mucus in patients with cystic fibrosis and is therefore an effective method of home physiotherapy. Patients with cystic fibrosis should be assessed as to which method suits them best.
BACKGROUND: In the airway of subjects with cystic fibrosis (CF) the combination of defective cAMP mediated chloride secretion and enhanced sodium absorption leads to dehydration of mucosal mucus and is reflected in an increased trans-epithelial potential difference (PD). The airway secretions may be less viscid and easier to expectorate if sodium (and water) reabsorption is inhibited. METHODS: To evaluate the response to sodium blocking agents, changes in the nasal PD in 20 transgenic CF mice were compared with 14 control mice (MF1 strain) before and after administration of nebulised amiloride and loperamide (both in a concentration of 1 mmol/l). The duration of action for both drugs was also determined after a single inhaled dose of 1 mmol/l for two minutes. RESULTS: The median basal PD was -24 mV in controls and -28 mV in CF mice (p < 0.01). This fell in CF mice after amiloride and loperamide administration by 15 mV and 14 mV, respectively, compared with a decrease of 7 mV and 5.5 mV in controls (p < 0.01). There was no further change in PD when loperamide was given after amiloride. This suggests that loperamide and amiloride may act on sodium absorption via similar mechanisms. Loperamide had a longer duration of action after a single administration than amiloride. CONCLUSION: The administration of amiloride and loperamide reduces the transepithelial potential and inhibits sodium reabsorption in the CF mouse airway. Further studies are required to determine if the more prolonged action of loperamide could be of therapeutic use.
PURPOSE: To evaluate the diagnostic accuracy of chest computed tomography (CT) in the prediction of a nonbronchial systemic arterial supply in patients with massive hemoptysis. MATERIALS AND METHODS: Forty consecutive patients with massive hemoptysis underwent contrast material-enhanced CT. Massive hemoptysis was defined as the expectoration of 300-600 mL of blood per day. Two CT features were considered to be suggestive of a nonbronchial systemic arterial supply: (a) pleural thickness of more than 3 mm adjacent to the parenchymal lesion and (b) enhancing vascular structures within the extrapleural fat layer. Conventional angiography was used as the standard of reference. CT scans were evaluated by two radiologists in consensus. The CT findings were compared with those of conventional angiography. The sensitivity, specificity, predictive values, and accuracy of CT for predicting the presence of a nonbronchial systemic arterial supply were assessed. RESULTS: In the determination of a nonbronchial systemic arterial supply, CT had a sensitivity of 80%, specificity of 84%, positive predictive value of 73%, negative predictive value of 91%, and accuracy of 84%. Sensitivity was highest for predicting the branches of subclavian and axillary arterial supply and was lowest for predicting the internal mammary arterial supply. Specificity and accuracy were highest for predicting the intercostal arterial supply. CONCLUSION: CT demonstrates acceptable sensitivity, specificity, and accuracy in the prediction of a nonbronchial systemic arterial supply in patients with massive hemoptysis.
From purulent cystic fibrosis (CF) sputum, previous investigators partially purified a trypsinlike protease. A similar purified enzyme is available commercially as "human sputum trypsin." To explore the nature and origin of this preparation, we purified and NH2 terminally sequenced its major protein component. The resulting sequence, Ile-Val-Gly-Gly-Tyr-Thr-(Cys)-Ala-Ala-Asn-Ser-Val/Ile-Pro-Tyr-Gln-Val -Ser-Leu-Asn-Ser, differs from known human proteins but is identical to porcine trypsin, including the Val/Ile polymorphism at residue 12. Specific activity and electrophoretic and inhibition profiles and immunoreactivity of sputum and porcine pancreatic trypsin are nearly identical. Because porcine trypsin is a major ingredient of digestive enzyme supplements taken by CF patients with pancreatic dysfunction, we propose that one or more lots of human sputum trypsin derive from enzyme supplements and are of porcine origin. The path by which trypsin ends up in sputum is unknown. Because sputum trypsin is active but susceptible to inactivation by plasma alpha1-proteinase inhibitor, it is unlikely to derive from trypsin absorbed into the bloodstream. However, it may originate from tracheally aspirated stomach contents or from digestive supplement-contaminated saliva mixed with expectorated sputum. The imbalance between proteases and antiproteases in CF bronchial secretions allows trypsin to remain active despite sensitivity to serpins and secretory leukocyte proteinase inhibitor. Furthermore, because sputum trypsin activates human progelatinase B, it may be responsible in part for the reported presence of activated matrix metalloproteinases in CF sputum.
To investigate the effect of oral sensory stimulation on cephalic phase insulin release (CPIR) and other compounds associated with glucose metabolism, a modified sham feed was used in which male subjects (n = 15) tasted, chewed, and then expectorated the food stimulus. Subjects remained fasted, sham fed, or ingested food on separate days over a 5-day period. After four baseline blood samples, poststimulus samples were taken every 2 min for 14 min and then every 15 min for 2.25 h. Increases in plasma insulin and C-peptide were found during the cephalic phase time period (0-10 min poststimulus) on the sham-fed and fed conditions when compared with fasted values. Glucose, norepinephrine, epinephrine, and free fatty acids were not affected by oral sensory stimulation or food ingestion during the cephalic phase period. The magnitude and profile of CPIR were similar after sham feeding and food ingestion. This study demonstrates that oral sensory stimulation can elicit CPIR in humans independently of changes in blood glucose.
Airway injury is a frequent result of the inhalation or aspiration of toxic material. Although upper airway damage can be identified endoscopically, pathophysiological changes are difficult to evaluate. This paper describes an animal model in which changes in tracheal blood and lymph flow rates, wet-to-dry weight ratios, and lymph-to-plasma protein ratios can be evaluated after injury. In this model, 12 cm of the cervical trachea were isolated using a double-cuffed endotracheal tube and injured with cotton smoke at near room temperature. Injury to the trachea was evaluated in twenty-five anesthetized sheep 4 (n = 3), 8 (n = 3), 24 (n = 3), 48 (n = 3), 96 (n = 3), and 192 (n = 2) h after smoke exposure and compared with sham control animals (n = 8). A significant increase in tracheal venous blood flow from 1.3 +/- 0.4 (SD) ml.min-1.cm-1 for the noninjured trachea to 2.8 +/- 1.2 was noted 24 h after injury (P less than 0.01). Lymph flow significantly increased from 1.3 +/- 0.4 microliters.min-1.cm-1 for the noninjured trachea to 9.8 +/- 3.3 24 h after injury while wet-to-dry weight ratios were elevated from 3.0 +/- 0.2 for noninjured trachea to 4.6 +/- 0.9 from 4 to 24 h after injury (P less than 0.01) and decreased to 3.7 +/- 0.5 by 96 h. Cast material consisting of airway exudate, cellular debris, and intact ciliated epithelial cells was both expectorated and found in the trachea when the animals were killed.(ABSTRACT TRUNCATED AT 250 WORDS)
A simple, rapid, and reliable TLC method for the separation and determination of sanguinarine has been established. This intensively studied biologically active alkaloid has a wide range of potentially useful medicinal properties, such as antimicrobial, antiinflammatory, and antitumoral activities. Sanguinarine has also been incorporated into expectorant mixtures and has a strong bactericidal effect upon gram-positive bacteria, particularly Bacillus anthracis and staphylococci. These medicinal properties are due to the interaction of sanguinarine with DNA. A fibre-optic-based fluorescence instrument for in situ scanning was used for quantitative measurements. The sanguinarine was determined over the range 5-40 ng and a detection limit of 1.60 ng. The method was applied to the quantification of sanguinarine in tissue culture extracts of Chelidonium majus L.
Plastic bronchitis is a rare complication in which bronchial casts of lymphatic origin develop in the tracheobronchial tree and cause airway obstruction. The main feature is expectoration of bronchial casts. This condition usually occurs in the postoperative period after the Fontan operation for congenital heart disease. Treatment modalities include mucolytics and chest physiotherapy, and in the most severe cases bronchoscopy to remove the casts and aerosolized urokinase or r-TPA. We describe a 12-year-old boy with pulmonary atresia with intact ventricular septum and severely hypoplastic right ventricle who underwent a modified Fontan operation at the age of 7 years. At the age of 12 years the patient started to present frequent episodes of coughing, dyspnea, and desaturation followed by difficult emission of white bronchial casts. An extracardiac Fontan conversion was performed to improve hemodynamics and symptoms. During the postoperative period frequent episodes of airway obstruction required bronchoscopy and finally improved with administration of aerosolized urokinase.
We report a case of multiple cavitary pulmonary metastases of gallbladder cancer. Radiologically, every cavity displayed a very thin wall containing only air inside. The postmortem histopathological examination showed that: (1) the cavities were surrounded by normal alveoli; (2) these walls were composed mostly of adenocarcinoma cells; (3) necrotic or mucous substance was sparse in the cavity space; (4) cancer cells infiltrated along the surface of the alveolar septa, and (5) the morphology of the cancer cells of the gallbladder and the lung was the same. It seemed likely that the thin-walled cavities in the lung might result from central breakdown of the tumor and subsequent expectoration of debris through the connected airways.
BACKGROUND AND OBJECTIVES: The changes of clinical symptoms and the tolerability of Prospan((R)) acute Effervescent Cough Tablets were investigated in a multicenter, prospective post-marketing surveillance (PMS) study focusing on patients with chronic bronchitis. PATIENTS AND METHODS: The study included 1,350 male and female patients aged 4 years and above who were treated in one of 135 participating medical practices and who suffered from chronic bronchitis (with or without airway obstruction). During a scheduled observational period of 4 weeks, the patients had to take 1(1/2) or 2 tablets per day (depending on their age), according to the manufacturer's dosing recommendations, corresponding to 97.5 or 130 mg of dried ivy leaf extract (about 585- 780 mg of drug). Treatment success was assessed by observing the changes in the direct symptoms of chronic bronchitis between the baseline examination and the end of treatment. Safety was evaluated by analyzing adverse events. RESULTS: In comparison to baseline, the following percentages of patients showed improved symptoms or were cured at treatment end: cough 92.2%; expectoration 94.2%; dyspnea 83.1%; respiratory pain 86.9%. In each of the four symptoms at least 38% of the initially affected patients were completely free of complaints. Three patients (0.2%) experienced adverse events in which a causal relationship to the drug under investigation could not be excluded (2x eructation, 1x nausea). CONCLUSIONS: Considering the favorable changes in all investigated clinical symptoms as well as the excellent tolerability in children and adults, the ivy leaf extract preparation Prospan acute Effervescent Cough Tablets can be considered as a therapeutic option in alleviating the symptoms of chronic bronchitis.
BACKGROUND: Recently the role of bacteria in acute exacerbations of chronic bronchitis (AECB) as well as antibiotic treatment with selected drugs, especially fluoroquinolones, have been better defined. OBJECTIVE: To assess the efficacy and safety in patients with AECB of prulifloxacin in comparison with ciprofloxacin. METHODS: AECB was defined according to the guidelines for the evaluation of new anti-infective drugs for the treatment of respiratory tract infections (1992). 235 patients took part in the trial; 117 (88 males and 29 females, mean age 64.8 years) received 600 mg prulifloxacin once daily and 118 (91 males and 27 females, mean age 64.5 years) 500 mg ciprofloxacin twice a day, for a duration of 10 days. The study design was randomized, multicenter, double-blind, double-dummy. Efficacy evaluations were performed by comparing pretreatment and posttreatment assessments. The clinical response was determined by 4-point rating scores on cough, dyspnea, and expectoration (volume and appearance). The microbiological response was assessed on sputum specimen. RESULTS: Clinical success was observed in 84.7 and 85% of patients in the prulifloxacin and ciprofloxacin groups, respectively. The 95% confidence interval proved the equivalence of treatments. Both drugs successfully eradicated the most commonly isolated strains, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Both treatments were well tolerated. Adverse drug reactions were always of mild or moderate intensity. CONCLUSION: The study showed that a 10-day course of prulifloxacin is as effective and safe as ciprofloxacin in the treatment of patients with AECB.
BACKGROUND/AIMS: Thyroid function impairment has been sporadically described in cystic fibrosis (CF) and ascribed to iodine overload or selenite deficiency. In this study we evaluated thyroid function in CF in order to verify these data and to evaluate if the modifications were related to serum levels of markers of inflammation and growth factors that we have previously shown to be altered in CF. METHODS: Seventeen young adult CF patients and 18 age-matched controls were enrolled in this study. The diagnosis of CF was confirmed by genetic analysis. None was treated with pulmonary expectorants. Serum IL-1beta, IL-6, TNF-alpha, IGF-I, IGF-II, IGFBP-2, IGFBP-3, TSH, fT3 and fT4 were measured using standard commercial kits. RESULTS: TSH, fT3 and fT4 serum levels were similar in CF patients and controls. Within the patient group, thyroid function did not vary in relation to C-reactive protein serum levels, respiratory function and clinical conditions (Shwachman score). No correlation was found with any growth factor or cytokine analyzed. CONCLUSIONS: At variance with the few previously published data, we did not detect any difference in thyroid function in patients with CF compared with normal healthy subjects. This could be due to the fact that no iodine overload or selenite deficiency was present in our patients. Thyroid function seemed independent of markers of inflammation and IGF-IGFBP serum levels.
The authors report a 48-year-old white male with lung cancer who was admitted to their clinic with a 1-year history of cough and shortness of breath. The patient was hospitalized because of progression of his complaints over 1 month. On the 3rd day of hospitalization, he expectorated a piece of gauze. The authors performed a fiber-optic bronchoscopy and saw pieces of gauze originating from granulation tissue located in the angle of the lower trachea and left main bronchi. A detailed anamnesis revealed that a mediastinoscopy had been performed 3 years ago for lung cancer staging: the gauze had migrated from the mediastinum to the endobrochial space.