Laryngeal cancer: long-term follow-up of respiratory functions after laryngectomy

Pulmonary function of 31 heavy smokers with laryngeal cancer was evaluated before and during the 1st year after total (n = 21) and conservative (n = 10) laryngectomy. 2 of them died because of recurrences, 1 for bronchopulmonary complications. Long-lasting hoarseness was the only presenting symptom in all patients. Preoperative lung function data and mucociliary clearance were consistent with a coexisting chronic obstructive lung disease in most subjects and was probably due to smoking. No differences were observed comparing pre- and postoperative data in the 10 conservative laryngectomy patients. On the contrary, the total-laryngectomy patients showed a progressive impairment of bronchial obstruction and bacteriological infection of the trachea during the 1st year after the operation. An impressive increase in mucociliary clearance rates has been observed 2 months after total laryngectomy during the postoperative hypersecretory phase. the obtained data allow us to hypothesize that when clinical conditions of laryngectomized patients in whom local or distant recurrences have been excluded deteriorate, this is related to a progressive bronchial obstruction at any level of the bronchial tree due to descending bacterial infection of the airways. To our knowledge this is the only work demonstrating that total laryngectomized patients need a complete pre- and postoperative evaluation of lung function, airway dynamics, mucociliary function and tracheal bacteriology for long-term prognosis and treatment.     

Mucociliary clearance in patients with chronic bronchitis and bronchial carcinoma

We measured the mucociliary clearance rates and lung function data of 40 normal subjects, of 30 smokers with chronic bronchitis and of 64 patients with bronchial carcinoma. The mucociliary clearance rate of cancer patients was significantly lower than that of normal subjects and of patients with chronic bronchitis who smoked the same amount of cigarettes. The fast clearing phase of the central bronchial tree is more delayed than the peripheral mucociliary clearance rate in smokers with and without carcinoma. With our mucociliary clearance measurement we assessed the self-cleaning filter function of about the first 10 generations of the branching bronchial tree where also most bronchial carcinomas develop. The correlation between lung function data (MMEF) and smoking habits is much better (r = 0.73) than with the measured mucociliary clearance rates (r = 0.3), suggesting that inborn errors of mucociliary transport are nearly as important as external lung damage due to smoking and infection in the development of chronic bronchitis and bronchial carcinoma.     

Ability for physical work of patients with newly-diagnosed destructive pulmonary tuberculosis

To find a relationship between a decrease in physical working capacity and the nature of bronchial tree lesions and the degree of bronchial obstruction, 124 patients with newly diagnosed destructive pulmonary tuberculosis were examined. The studies demonstrated that the physical capacity for work depended on the extent of bronchial tree lesions, the severity and extent of bronchial obstruction. A maximum decrease in the physical capacity for work is observed in bilateral diffuse endobronchitis and the most severe bronchial obstruction. A decrease in the physical capacity for work of the 2-nd and 3-rd degrees is, as a rule, significantly observed with minor bronchial and generalized obstructions.     

The role of mucociliary dysfunction in bronchial asthma.

Abnormalities of mucociliary function in the airways of patients with bronchial asthma are suggested by the clinical observation of excessive tracheobronchial secretions which are difficult to expectorate and may contribute to bronchial obstruction. Pathologic and functional studies in animals and patients have demonstrated an impairment of mucociliary transport mechanisms, but the pathogenesis of this abnormality is still poorly understood. In patients with allergic asthma, the elaboration of chemical mediators in the lung seems to depress mucociliary function. Although pharmacologic agents which increase mucous transport rates have been identified, more potent stimulators will probably be needed to produce a clinical improvement in patients with bronchial asthma.     

The effect of bronchial obstruction on central airway deposition of a saline aerosol in patients with asthma

We studied the effect of bronchial obstruction on central airway deposition of a 0.9% saline aerosol (MMAD = 1.12 micron; sigma g = 2.04) labeled with 99mTc sulfur colloid. Radioaerosol was inhaled on 2 occasions by 8 patients with asthma. The degree of bronchial obstruction at the time of radioaerosol inhalation was measured by the FEV1. Mucociliary clearance of the radioaerosol was used as an index of regional aerosol distribution, because clearance from the densely ciliated central airways occurs more rapidly than from the peripheral, nonciliated regions of the lung. Using the Weibel lung model and an average mucociliary clearance rate of 1 mm/min, we determined that clearance of the radioaerosol from lung generations 1 to 5 (central airways) would be complete within approximately 90 min. Central airway deposition was therefore quantified as radioaerosol clearance in 97 min using a gamma camera. On Days 1 and 2, clearance ranged from 0 to 45% and from 0 to 17%, respectively; FEV1 as a percent of predicted FEV1 ranged from 36 to 88 on Day 1, and on Day 2 from 54 to 92. Radioaerosol clearance was inversely correlated with the baseline FEV1, with r = -0.7673 (linear regression analysis; p less than 0.05). These data suggest that the magnitude of bronchial obstruction is a determinant of aerosol distribution within the lung of patients with asthma and that increased bronchial obstruction enhances central airway deposition of inhaled particles.     

Action of tulobuterol and fenoterol on the mucociliary clearance

The influence of tulobuterol and fenoterol upon mucociliary clearance (mC) and airway obstruction was investigated in 8 patients with chronic obstructive bronchitis and two patients with chronic bronchial asthma. The lung function and mC measurements were repeated after a 1-week random oral treatment with 4 mg tulobuterol/day or 7.5 mg fenoterol/day in a double-blind cross-over design. Tulobuterol and fenoterol improved mC of the total, central and peripheral bronchial tree significantly in comparison to the pretreatment values (p less than 0.001) reaching, after beta 2-agonist therapy, values observed in normal subjects. In comparison to no treatment and pretreatment with oral fenoterol, tulobuterol protected slightly better from the inhalative provocation with 99mTc radioactive erythrocytes used to measure mC. Inhalative fenoterol was more efficient than oral fenoterol or tulobuterol to reverse the bronchospastic part of airway obstruction. No differences of mean daily peak flows, systolic and diastolic systemic blood pressure measurements and pulse rate were recorded during tulobuterol and fenoterol treatment. Both drugs were tolerated without side effects.     

Effects of drugs and environmental factors on ciliary movement (author's transl)]

The effects of a number of drugs, potassium and calcium ions, and air humidity on mucociliary function were studied in isolated preparations of rats bronchial tree. Adrenergic drugs increased the rate of ciliary beat significantly. Cilioexitation also occurred, though to a smaller degree, after application of acetylcholine, pilocarpine, aminophylline, prednisolone, KI and NH4C1. Serotonin, histamine, and acetylcystein did not change ciliary frequency to any significant degree; however, histamine in high concentrations caused ciliary incoordination. Codein and normetadon, nicotine and pentobarbital had a dose-dependent ciliodepressive effect. However, small concentrations of nicotine and pentobarbital were slightly stimulative. Methysergid and phentolamine were slightly ciliodepressive. Alterations of the concentrations of calcium and potassium ions in the nutritive solution influenced ciliary frequency but had no effect on other characteristic features of the ciliary movement. The ciliated epithelium of the bronchial tree could be irreversibly damaged by air having low relative humidity.     

The effect of systemic hydration on normal and impaired mucociliary function

Whether systemic hydration enhances the clearance of lower airway secretions in normal lungs and in lungs during antigen-induced bronchial obstruction was studied. In five conscious allergic sheep, tracheal mucus velocity (TMV) as an index of lower airway mucociliary clearance was measured before and serially for 60 minutes following intravenous infusion of 5% dextrose solution at volumes ranging from 5 to 35 ml/kg. None of these fluid regimens had a significant effect on TMV, although there was a tendency toward a slowing of TMV at the higher volumes of 25 and 35 ml/kg. After producing an acute allergic airway response by inhalation challenge with specific antigen, there was a decrease in mean TMV by 27% and 15% before sham infusion and infusion of 35 ml/kg of dextrose solution, respectively. During the subsequent 60-minute observation period, mucociliary transport was further impaired by dextrose infusion, with mean TMV being lower after dextrose infusion than after sham infusion at all times of measurement (P less than 0.05). The lowest value was reached 30 minutes after dextrose infusion (45% of control). It was concluded that systemic hydration does not significantly alter airway mucociliary transport in the normal state but further impairs mucociliary transport during allergic mucociliary dysfunction. This raises questions regarding the therapeutic role of systemic hydration in the treatment of children and adults who have bronchial asthma.     

Empfindlichkeitssteigerung der Bronchialmuskulatur durch proteolytische Fermente im Sputum

The proteolytic enzyme containing sputum may increase the sensitivity of the cholinergic broncho-constrictory receptors to a great extent. Enzyme inhibitors are also detected in sputum. These inhibitors can protect the cholinergic receptors in the bronchial tree against the effect of proteolytic enzyme. The influence of acetylcholine on obstruction of the air passage in chronic obstructive bronchitis, as well as allergic air passage obstruction, is of decisive importance. The hypersensitivity of the cholinergic receptors in the bronchial tree plays a significant role in this group diseases.     

Mucociliary clearance following tracheal resection and end-to-end anastomosis

Mucociliary clearance is an important cleaning system of the bronchial tree. The complex transport system reacts sensitively to medicinal stimuli and inhaled substances. A disturbance causes secretion retention which encourages the development of acute and chronic pulmonary diseases. It is not yet known in which way sectional resection of the central airway effects mucociliary clearance. A large number of the surgical failures are attributable to septic complications in the area of the anastomosis. In order to study the transportation process over the anastomosis, ten dogs underwent a tracheal resection with end-to-end anastomosis, and the mucociliary activity was recorded using a bronchoscopic video-technical method. Recommencement of mucous transport was observed on the third, and transport over the anastomosis from the sixth to tenth, postoperative days. The mucociliary clearance had completely recovered on the twenty-first day in the majority of dogs. Histological examination of the anastomoses nine months postoperatively showed a flat substitute epithelium without cilia-bearing cells in all dogs. This contrasts with the quick restitution of the transport function. In case of undamaged respiratory mucosa, a good adaptation of the resection margins suffices for the mucous film to slide over the anastomosis.     

Central hemodynamic changes in the early stages of the development of cor pulmonale

Changes in central hemodynamic parameters in response to acetylcholine aerosol inhalations were evaluated in 60 patients with chronic obstructive bronchitis and 17 normal male subjects. In patients with chronic bronchitis, induced bronchial obstruction was accompanied with increased heart rate and stroke volume as well as circulation shift to a hyperdynamic regimen with a rise in minute volume and systemic arterial blood pressure. There was no direct correlation between the degree of bronchial obstruction and the increment in cardiac output. The increase in cardiac output was however shown to be significantly higher in individuals who responded to acetylcholine inhalation with an at least 20% drop in forced exhalation within 1 second, as compared to less sensitive patients, while the rate of hyperdynamic response was dependent on the severity of pre-inhalation bronchial obstruction.     

Acute bronchial obstruction in sheep: histopathology and gland cytokine expression

An ovine model of smoke inhalation and burn (S+B) injury models the pathophysiology of these injuries in humans. This study examines the degree of airway obstruction, associated histopathology, and bronchial gland cell expression of cytokines during the first 24 hours after S+B injury in sheep. Changes in the mean degree of obstruction were limited to the bronchial airways, showing significant increases in obstruction with time, P<.05. At 4 hours after injury, the obstructive material was predominantly mucus, with neutrophils clustered around and within gland acini. At 8 to 24 hours, bronchial obstruction was characterized by increased inflammatory cell accumulation. Immunohistochemical results showed that gland cells constitutively express and secrete interleukin (IL)-1beta, and that after injury there is an increase in the percentage of gland cells staining for IL-1alpha, IL-8, and tumor necrosis factor (TNF)-alpha, P<.05.     

Diagnostic value of the forced oscillation test in detection of bronchial obstruction

Clinical testing of the forced oscillation test (FOT) yielded criteria for bronchial obstruction: an increase in viscous respiratory resistance (VRR) (Rfo, Rin, Rex); the frequency dependence of VRR; and a decrease in a phase angle. The study of VRR promoted detection of bronchial malpatency in additional 20.7% of the individuals who had no bronchial obstruction, as evidenced by spirography (SG) and forced expiration volume-current curve (FEV-CC) recording. To improve the diagnosis of bronchial patency impairments, it is expedient to use FOT of VRR along with the routine methods (SG and FEV-CC recording). A relationship has been established between the values of VRR and the clinical signs of chronic bronchitis and the degree of bronchial obstruction.     

Experimental models of asthma

Ideally, animal models of bronchial asthma should exhibit most if not all features of human bronchial asthma. The general aim of developing such animal models has undoubtedly been to reproduce the human disease in order to study its pathophysiology and pathogenesis. A careful review of the literature indicates that allergic bronchoconstriction in the guinea pig, dog, sheep, and monkey exhibit only some of the typical characteristics of bronchial asthma in man. In keeping with human asthma, allergic animals exhibit nonspecific airway hyperresponsiveness and physiologic responses to antigen challenge resembling those in man. Also, the immunologic pathways leading to bronchoconstriction and mucociliary dysfunction are essentially the same in allergic animals and patients with allergic bronchial asthma. On the other hand, spontaneous and persistent bronchial obstruction, typical features of human bronchial asthma, have not been observed in animal models. Likewise, the pathologic lesions of human bronchial asthma have not or only incompletely been reproduced in allergic animals. At the present state of our knowledge, one might therefore conclude that allergic bronchoconstriction in animals is an excellent model of antigen induced bronchoconstriction in man as it is observed in the laboratory, but a less satisfactory model of spontaneous bronchial asthma. The animal models represent useful research tools to study some pathophysiologic aspects of bronchial asthma as long as the limitations of the model are recognized. Which of the four currently used species is chosen for a given experiment and whether new models need to be developed depends upon the physiologic question to be answered.     

Does "pulmogenic hypertension" exist?

Validity of criteria of so called "pulmogenic hypertension" in chronic obstructive pulmonary diseases was assessed with the use of a questionnaire and simultaneous 24 hour monitoring of blood pressure and peak expiratory rate in 80 and 28 patients, respectively. This method of bifunctional monitoring allowed to study relationship between blood pressure level and degree of bronchial obstruction. The results did not confirm the presence of "pulmogenic hypertension" as a special form of arterial hypertension.     

Biodegradability of inhaled organic particles in patients with chronic bronchitis

2 h after the inhalation of monodispersed 99mTc-labeled autologous spherocytes and of commercial human albumin microspheres (HAM), 7 patients with chronic bronchitis underwent bronchofibroscopy. The fate of organic particles along the tracheobronchial tree was verified by scanning electron microscopy and the proteolytic activity (trypsin and PZ peptidase) in mucus samples was assessed. Significant proteolytic activity was detected in bronchial secretions. Thereafter in vitro digestion of labeled spherocytes and HAM was verified after exposure to increasing concentrations of trypsin. While in vitro a similar time-course of tryptic digestion of both particles was observed, in vivo spherocytes seem to be less vulnerable to enzymatic digestion. These findings add another unexpected variable, which may influence the reproducibility of radioaerosol lung mucociliary clearance measurements, and improve its standardization.     

Asthma patients' perception of dyspnea during acute bronchoconstriction

The aim of this study was to analyze variations in the perception of acute bronchial obstruction among asthmatics in our practice and to try to define the variables that influence inter-individual differences. We studied 153 asthmatics in stable condition, using a Borg scale to measure dyspnea perceived during a histamine bronchial challenge test. To study individual perception we analyzed both absolute magnitude of perception of dyspnea on the Borg scale when forced expiratory volume in 1 second (FEV1) fell 20% (perception score 20-PS20) and the mathematical difference between PS20 and baseline dyspnea (change in Borg, CB). The results were as follows. 1) The factors that affected PS20 according to multiple linear regression were anxiety, baseline dyspnea and the provocative concentration required to produce a 20% fall in FEV1 (PC20). 2) Within each level of asthma severity, there were differences in dyspnea perception when FEV1 fell 20% (analysis of variance of repeated measures), such that patients with mild asthma and no bronchial obstruction perceived more change in dyspnea. 3) CB during the bronchial challenge test distinguished four ways of perceiving dyspnea: 15% were dysperceivers, 13% were hypoperceivers, 48% were normoperceivers and 24% were hyperperceivers. 4) Hypoperceivers and dysperceivers were at greater risk of severe exacerbation whereas hyperperceivers requested unnecessary medical consultations. 5) Subjects with poorer quality of life were usually dysperceivers; hyperperceivers were the second most common type among those with poorer quality of life. In conclusion, a large percentage of asthmatics do not appropriately perceive acute bronchial obstruction, and the simplest way to evaluate their perception is to calculate the change in dyspnea (on a Borg scale) during the bronchial challenge test. The manner of perceiving dyspnea can not be predicted beforehand, yet it has a significant impact on the use of medical resources and patient quality of life, among other aspects.     

Status of the bronchi in patients with pulmonary tuberculosis and different haptoglobin phenotype]

External respiration function test and bronchologic examination were conducted in 206 pulmonary tuberculosis patients with different haptoglobin (Hp) phenotypes. It was found that obstructive changes in peripheral portions of the bronchial tree were most common and marked among the revealed disorders of pulmonary ventilation function. These changes promote a decrease in the ventilation reserve to a great extent. As compared to Hp 2-1 carriers, specific endobronchitis and bronchial obstruction symptoms were significantly more frequent in patients with Hp 2-2. Bronchial obstruction symptoms alone were twice as frequent as in patients with Hp 1-1 than in Hp 2-1 carriers. The findings indicate that there is a close relationship between the status of the bronchi in pulmonary tuberculosis patients and the genetically determined Hp phenotype.     

Influence of azelastine and some selected drugs on mucociliary clearance

The effect of azelastine and some selected compounds on ciliary beating frequency (CBF) was investigated in vitro using human mucosal samples and in vivo using anesthetized guinea pigs. Further influence of azelastine on mucus secretion was evaluated in mice and on mucociliary clearance in anesthetized rabbits. Azelastine influenced the ciliary beating frequency neither in vitro nor in vivo. Azelastine, similarly to salbutamol, ambroxol, and bromhexine, increased mucus secretion measured by the tracheal output of phenol red. Azelastine dose-dependently enhanced mucociliary clearance measured by elimination of ^99mTc-labeled erythrocytes in rabbits. The activity of azelastine proved to be about 10 times stronger than that of bromhexine. Since the ciliary activity remained unchanged under the influence of azelastine, it is likely that azelastine increases the mucociliary clearance by enhancing bronchial secretion. It is possible that the observed increase in mucociliary clearance may contribute to the beneficial effect of azelastine in the treatment of respiratory diseases. Offprint requests to: I. Szelenyi     

Morphological features of the interaction between mucus and surfactant on the bronchial mucosa

The secretion layer over the bronchial epithelium was investigated on human biopsy material. In the sol phase of the secretion, phospholipid membranes stretched out or arranged in vesicular structures could regularly be demonstrated. They displayed the same structure as the surfactant material in the alveolar space. It can be inferred therefrom that the surfactant is excreted via the bronchial system. It probably contributes to the stabilization of the sol phase of the mucus and thus influences the sliding capacity of the gel phase. So the surfactant has an important function in maintaining mucociliary clearance at the bronchial mucosa.