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Of 36 dogs with a history of chronic coughing or dysponea examined by bronchoscopy, eight were found to have parasitic tracheobronchitis. Oral treatment with the anthelmintic levamisole at a rate of 7.5 mg per kg bodyweight was found to be successful in every case.
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An expandable stainless steel stent was formulated for use in the treatment of tracheobronchial stenosis, tracheomalacia, and airway collapse following tracheal reconstruction. The stents were placed through an endotracheal tube into the trachea and bronchi of 11 healthy dogs. The stents expanded over time, substantially increasing the diameter of the lumen. Slight migration occasionally occurred, while an inflammatory reaction was noted in each animal. The stents were successfully used in the treatment of two cancer patients to dilate a postoperative bronchial stenosis that caused pneumonia and to support a tracheal graft that collapsed with respiration. Because of the stent migration in experimental studies, designs are being tested to develop stents with greater stability. These stents may be effective in overcoming stenosis caused by scarring, extrinsic compression, and collapse of reconstructed tracheobronchial structures.
Respiratory epithelial cells play a crucial role in the inflammatory response in endotoxin-induced lung injury, an experimental model for acute lung injury. To determine the role of epithelial cells in the upper respiratory compartment in the inflammatory response to endotoxin, we exposed tracheobronchial epithelial cells (TBEC) to lipopolysaccharide (LPS). Expression of inflammatory mediators was analyzed, and the biological implications were assessed using chemotaxis and adherence assays. Epithelial cell necrosis and apoptosis were determined to identify LPS-induced cell damage. Treatment of TBEC with LPS induced enhanced protein expression of cytokines and chemokines (increases of 235-654%, P < 0.05), with increased chemotactic activity regarding neutrophil recruitment. Expression of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was enhanced by 52-101% (P < 0.0001). This upregulation led to increased adhesion of neutrophils, with >95% adherence to TBEC after LPS stimulation, which could be blocked by either ICAM-1 (69%) or VCAM-1 antibodies (55%) (P < 0.05). Enhanced neutrophil-induced necrosis of TBEC was observed when TBEC were exposed to LPS. Reduced neutrophil adherence by ICAM-1 or VCAM-1 antibodies resulted in significantly lower TBEC death (52 and 34%, respectively, P < 0.05). Therefore, tight adherence of neutrophils to TBEC appears to promote epithelial cell killing. In addition to indirect effector cell-induced TBEC death, direct LPS-induced cell damage was seen with increased apoptosis rate in LPS-stimulated TBEC (36% increase of caspase-3, P < 0.01). These data provide evidence that LPS induces TBEC killing in a necrosis- and apoptosis-dependent manner.
In neurogenic inflammation, tachykinins trigger the adhesion of neutrophils and eosinophils to leaky venules. The goals of the present study were to determine whether this leukocyte adhesion is mediated by neurokinin type 1 (NK1) receptors and to determine whether the amount of leukocyte adhesion corresponds to the amount of plasma leakage. Anesthetized rats were injected intravenously with substance P, the NK1 receptor agonist [Sar9, Met(O2)11]-substance P, or the NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10). Five minutes later, the adherent neutrophils and eosinophils in blood vessels of the tracheal mucosa were stained histochemically and plasma leakage was quantified, as assessed by the extravasation of Monastral blue. Substance P and the NK1 agonist caused similar amounts of leukocyte adhesion, but the NK2 agonist had no effect. Pretreatment with the NK1 receptor antagonist CP-96,345 (4 mg/kg iv), before challenge with substance P, capsaicin, or aerosol hypertonic saline, reduced the amount of neutrophil adhesion by 56%, 93%, and 57% and reduced the amount of eosinophil adhesion by 70%, 83%, and 65%, respectively. Plasma extravasation was decreased by 89%, 95%, and 94%. The number of adherent neutrophils in the trachea was strongly correlated with the number of adherent eosinophils (r2 = 0.61). The greatest amount of leukocyte adhesion occurred in larger diameter venules than did the maximal amount of Monastral blue leakage. We conclude that NK1 receptors mediate the adhesion of neutrophils and eosinophils as well as the plasma leakage triggered by substance P, capsaicin, or hypertonic saline. This leukocyte adhesion evidently does not occur at exactly the same sites as the plasma leakage.
The present study was performed to determine whether neurogenic inflammation in the rat trachea can be exaggerated by inhibiting neutral endopeptidase, an enzyme that degrades tachykinins that are believed to mediate neurogenic inflammation. Neurogenic inflammation was produced by antidromic electrical stimulation of one vagus nerve (2.5 Hz, 1 ms, 5 V for 5 min) in the presence of atropine or by an intravenous injection of capsaicin (100 micrograms/kg). Neutrophils that adhered to the endothelium of venules were visualized and counted in tracheal whole mounts that were stained by a histochemical reaction for myeloperoxidase. Neural inflammation increased the number of adherent neutrophils. Pretreatment with the neutral endopeptidase inhibitor phosphoramidon (1.0 or 2.5 mg/kg iv) increased neutrophil adhesion induced by neural inflammation. As assessed by the amount of extravasation of Monastral blue pigment, neural inflammation also increased vascular permeability, and this change was potentiated by phosphoramidon. These results are consistent with the concept that neuropeptides released from sensory nerves in the tracheal mucosa cause neutrophils to adhere to venules and increase vascular permeability and that these effects are modulated by neutral endopeptidase.
Pulmonary complications occur in an estimated 0.21% of patients with inflammatory bowel disease. The most common presentation of pulmonary manifestations is large airway disease, such as tracheobronchitis, chronic bronchitis or bronchiectasis. Small airway disease, such as constrictive bronchiolitis or bronchiolitis obliterans with organizing pneumonia, is less frequently reported, and is described as occurring in isolation from large airway disease. A case of a postcolectomy ulcerative colitis in a patient who has both large airway involvement, tracheobronchitis and bronchiectasis, and constrictive bronchiolitis is presented.
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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.
The reactivity of cat tracheal smooth muscle to histamine in vitro was studied at various degrees of inflammation of the airways induced experimentally by the intratracheal administration of turpentine oil or Staphylococcus aureus, both in aerosol form. Tracheal smooth muscle preparations from the control animals did not respond to histamine in doses of 10(-9)-10(-3) mol X 1(-1). In tracheal preparations from three groups of cats with turpentine oil inflammation induced 24 h, 48 h and 15 days previously, histamine caused contractions in 20, 70 and 24% of the cats, respectively, according to the degree of inflammation. All tracheal preparations from cats with staphylococcal inflammation responded to histamine by contraction. Atropine, acetylosalicylic acid and phentolamine did not abolish histamine contractions in tracheal preparations, but clemastine did.
In the winter of 1972-1973 a multicentre trial of the treatment of upper and lower respiratory tract infections was carried out in Spain using doxycycline. 85 physicians participated in the study and treated 1,653 patients. The infections included acute bronchitis, acute exacerbation of chronic bronchitis, pneumonia, bronchopneumonia, tonsillitis, pharyngitis, trachetis, sinusitis, and otitis media. The majority of the patients were adult out-patients although some children and adolescents were included: 1,011 of the patients were male and 642 female. A number of the signs of respiratory infection such as temperature, cough, pain and inflammatory symptoms were examined. A rapid reduction in intensity and severity was noted in all of these parameters. Tolerance to the antibiotic was excellent. Only minor side-effects were reported and these were mild and mainly limited to the gastro-intestinal tract - in no case was treatment discontinued. The total number of side-effects was 37; they occurred in 31 out of the 1,653 patients. The overall evaluation of results showed a very good or good response in 85% of the patients. It appears from this multicentre study that the efficacy of doxycycline has in no way decreased over the 7 years of its extensive use in Spain. It remains a fast acting and effective antibiotic in upper and lower respiratory tract infections irrespective of age, sex or diagnosis.
In the winter of 1973-4, general practitioners from seven European countries took part in a multi-centre trial of doxycycline in the treatment of infections of the respiratory tract. The carefully designed protocol was observed by all participants. A total of 1,747 patients were admitted to the trial; their ages ranged from 6 years to over 80. The commonest diagnoses (50%) were acute bronchitis and acute exacerbations of chronic bronchitis. On the recommended dosage of 200 mg doxycycline on the first day, followed by 100 mg daily thereafter (though 200 mg could be continued daily in severe cases), 87% of patients achieved good or very good results. Both subjective (pain) and objective (sputum volume and viscosity, temperature, cough) measures showed rapid improvement, usually by the third to fifth days. Side-effects were minimal and mainly gastrointestinal and caused only 4 patients to discontinue treatment. Overall, doxycycline proved its effectiveness and rapidity of action.
23 physicians in Italy took part in a multi-centre clinical trial of doxycycline in the treatment of respiratory tract infections. The case records of 290 patients were assessed with respect to both subjective and objective improvement and clinical cure: most patients were considered improved by the third day and cured by the fifth. The recommended dose of doxycycline was 200 mg on the first day and 100 mg daily thereafter; only 11 of the patients had to continue treatment beyond the tenth day. The antibiotic was extremely well tolerated; gastrointestinal side-effects occurred in 10 patients. Overall, 88.6% of the patients achieved a very good or good result.
A multi-centre general practitioner trial was carried out in the Netherlands during the winter of 1973/1974. This trial was part of a larger pan-European study. There were 13- cases studied in the Netherlands who were only treated with doxycycline, by 17 physicians. All patients included in the trial had an acute infection of either the upper or lower respiratory tract. tthere were 64 females and 66 males. The results were excellent at 100 patients (76.9%) had a very good result, 21 patients (16.2%) had moderate or fair results, and only 7 patients (5.4%) had poor or negative results. Doxycycline was well tolerated as no side-effects were noted in 122 of the patients (93.8%). In the 8 patients who experienced side-effects they were mild and self-limiting.
Reference is made to the results obtained in 24 children, from 11 months to 12 years, affected with acute pneumopathies and treated with fosfomycin with a dosage of 200 mg/kg/day. In all cases a clinical, radiological, biological and bacteriological study was carried out. At the same time, levels of fosfomycin in plasma and sputum were checked every 5 days during the course of treatment. In the 4 cases of pleurisy the level of antibiotic in the pleural liquid was also checked. The concentration of fosfomycin in the sputum gives very variable results with average values oscillating between 16.5 and 23.4% of the plasmatic level respectively at the beginning and end of treatment, a cumulative effect of the antibiotic being observed. Concentration in pleural liquid oscillates between 39 and 50%. The clinical, radiological and biological evolution has been favourable iin 21 cases, unfavourable in two cases and in one case treatment had to be suspended because of the apparition of a cutaneous necrosis. Apart from this case no notable toxic effects were observed. Children do not support intramuscular injections very well and intravenous injections often cause phlebitis.
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