A novel charcoal-induced model of obliterative bronchiolitis-like lesions: implications of chronic nonspecific airway inflammation in the development of posttransplantation obliterative bronchiolitis

OBJECTIVES: In this study, we describe the development of a nonallogeneic animal model of obliterative bronchiolitis-like lesions. Furthermore, we examined whether chronic rejection alone can lead to the development of obliterative bronchiolitis or whether additional nonspecific airway inflammation is required. METHODS: Part I: Rats were intratracheally injected with 0.2 ml of activated charcoal or sorbitol solution (carrier for charcoal control). Animals were put to death beginning at 2 weeks up to 20 weeks. Part II: Animals were divided into three groups: group I, underimmunosuppressed Brown Norway to Lewis lung allografts; group II, charcoal-treated underimmunosuppressed allografts; and group III, charcoal-treated rats. Animals were put to death at 3 months after transplantation. RESULTS: Part I: In charcoal-laden bronchioles, subacute nonspecific airway inflammation was detected at 2 weeks. Slow, subclinical fibroproliferation ensued during the following weeks. Obliterative bronchiolitis-like lesions were observed in 80% of charcoal-treated animals at 12 weeks. Part II: Allografts developed extensive vascular lesions consistent with acute and chronic vascular rejection. Obliterative bronchiolitis-like lesions were scarcely detected. Charcoal-treated allografts demonstrated evidence of diffuse and severe obliterative bronchiolitis-like lesions. CONCLUSIONS: Transtracheal injection of activated charcoal into native lungs results in slowly progressive airway injury and inflammation leading to obliterative airway lesions. Inadequate immunosuppression primarily results in chronic vascular rejection but not obliterative bronchiolitis. Underimmunosuppressed allografts subjected to nonspecific airway inflammation develop obliterative airway lesions that are more prominent than in native lungs. This suggests that a cofactor to chronic rejection is likely necessary for the development of lung transplant obliterative bronchiolitis.     

Aspects of chronic airflow obstruction

This report questions several commonly used definitions and commonly accepted concepts. It suggest that the term, "chronic airflow obstructions," should replace the terms, "chronic obstructive pulmonary disease," "chronic obstructive lung disease," or "chronic airway obstruction," because it is flow that is obstructed. It is suggested the term, "chronic mucous hypersecretion," be used, rather than "chronic bronchitis," and that the latter be avoided. Chronic bronchitis should not be equated with narrowing of the airway and emphysema with loss of elastic recoil. Chronic bronchitis, emphysema, and lesions of the small airways probably occur together more frequently than chance will allow because of a common etiologic agent, tobacco smoke. Chronic mucous hypersecretion without other airway or parenchymal lesions seldom produces airflow obstruction and does not impair prognosis significantly. Central airways are important in chronic airflow obstruction. It is time that someone found out what is happening in subjects with abnormal results on tests of the function of small airways. The definition of "destruction" as it occurs in emphysema is deceptive, and loss of recoil and emphysema may be separate conditions. The dysfunction that occurs in emphysematous lungs is due mainly to associated airway lesions and may perhaps be due in part to the site and nature of emphysematous lesions (as opposed to loss of elastic recoil).     

Metastatic melanoma from intraocular primary tumors: the Southwest Oncology Group experience in phase II advanced melanoma clinical trials

BACKGROUND: Tracheal neoplasms are extremely rare, representing only 0.2% of malignancies of the respiratory tract. A case of tracheal chondrosarcoma, with airway obstruction, seen in the Department of Otolaryngology Head and Neck Surgery at the University of Cincinnati is presented. Review of the literature was undertaken, revealing 10 previously described cases. Clinical presentation and treatment options are described. METHODS: A literature review of all reports of tracheal chondrosarcoma was undertaken. RESULTS: From this review, we identified only 10 single case reports. The majority of patients were elderly men, with lesions in the mid to distal trachea. Treatment predominantly consisted of tracheal resection. Recurrence was associated with failure to achieve complete resection. CONCLUSIONS: We conclude that tracheal chondrosarcoma is an exceedingly rare upper airway neoplasm. Treatment should be aimed at complete surgical removal.     

Our experience in treating obstructive lesions of the main airway by Nd-Yag laser resection

We performed 164 laser resections with a neodymiumyttrium-aluminum-garnet (Nd-Yag) laser in 116 patients between January 1992 and December 1997. Seventy-eight patients had malignant neoplasms, 5 had neoplasms of intermediate malignancy and 33 had inflammatory tracheal lesions. Eighteen resections were emergency procedures. All resections were performed with the patient under general anesthesia and preferably breathing spontaneously. Immediate results varied according to the nature and location of the lesion. Treatment was palliative for tumors showing intraluminal proliferation, providing successful reopening of the airway as shown endoscopically in 70% of patients. Mean survival of the 44 patients with malignant lesions who could be followed was 29 weeks, with a median of 15.19 (range, 1-120). The tracheas of patients with inflammatory stenosis were reopened rapidly and emergency tracheostomy was avoided in all cases. One patient with malignant tracheal tumors died during the procedure due to asphyxia related to tracheal hemorrhage.     

Bronchial hyperresponsiveness after cervical spinal cord injury

Cervical spinal cord injury results in interruption of sympathetic airway innervation, which originates from the upper thoracic spine, whereas parasympathetic nerve supply, arising in the vagal nuclei of the brainstem, remains intact. To assess the effect of such an altered neural environment on airway reactivity, bronchoprovocation testing was performed on eight subjects with nonacute traumatic lesions of the cervical spine, all of whom were lifetime nonsmokers without history of respiratory symptoms prior to their injury. Bronchial challenge was subsequently repeated after pretreatment with the anticholinergic agent, ipratropium bromide, an inhibitor of airway muscarinic receptors. All subjects demonstrated hyperresponsiveness to methacholine (the concentration of methacholine producing a fall in FEV1 of 20 percent from baseline [PC20] = 1.42 +/- 1.61 [SD] mg/ml). Airway hyperreactivity was completely blocked by pretreatment with inhaled ipratropium bromide (mean PC20 > 25 mg/ml [p < 0.0001]). The bronchial hyperresponsiveness observed in this population most likely reflects the loss of sympathetic airway innervation and resultant unopposed cholinergic bronchoconstrictor tone which results from transection of the cervical spine. Blockade of methacholine hyperresponsiveness with ipratropium bromide suggests a muscarinic receptor-mediated phenomenon.     

Laryngeal Kaposi's sarcoma in patients with AIDS

Over a period of 10 years 17 human immunodeficiency virus(HIV)-infected patients with laryngeal Kaposi's sarcoma were seen and treated at University College London Hospitals. All patients had advanced HIV disease. Their presentation was with symptoms of upper airway obstruction in the majority of cases and the diagnosis was made by fibreoptic examination of the larynx. Biopsy was associated with brisk haemorrhage in one patient, who required a temporary tracheostomy, and was not performed in the other 16 cases. The commonest site of laryngeal involvement was the supraglottis in 11 patients, with glottic lesions noted in eight patients: subglottic lesions were seen in only three. Treatment of laryngeal Kaposi's sarcoma was, in general, conservative, five patients received low dose radiotherapy to the larynx and 10 were treated with systemic chemotherapy for disseminated Kaposi's sarcoma. Laryngeal Kaposi's sarcoma did not contribute to patient mortality.     

Histological indications of a progressive snorers disease in an upper airway muscle

The etiology of upper airway collapsibility in patients with snoring and obstructive sleep apnea (OSA) remains unclear. Local muscular abnormalities, including neurogenic lesions, could be a contributory factor. The aim of this study was to histologically evaluate the hypothesis of a progressive snorers disease. Biopsies of palatopharyngeal muscle were obtained from 21 patients with habitual snoring and different degrees of upper airway obstruction (10 patients with OSA) and 10 nonsnoring control subjects. Morphological abnormalities, including neurogenic signs (e.g., type grouping), were blindly quantified. The degree of abnormality was significantly increased in patients compared with control subjects. The individual score of abnormalities was significantly correlated to the percentage periodic obstructive breathing but not to oxygen desaturation index. Analyses of the individual fiber-size spectra demonstrated a significantly increased number of hypertrophied and/or atrophied fibers in patients compared with controls. The subjects were also divided into three groups according to their type of nocturnal breathing, i.e., nonsnorers, patients with < 20%, and patients with > or = 45% obstructive breathing. These groups correlated significantly with the degree of abnormality and pathological fiber-size spectra. In conclusion, these results support the hypothesis of a progressive local neurogenic lesion, caused by the trauma of snoring, as a possible contributory factor to upper airway collapsibility.     

Unequal cleavage in the early Tubifex embryo

The objective of this study was to generate and characterize monoclonal antibodies against rat airway mucins. Therefore, it should serve as a useful tool in studying the regulation of airway mucins using various in vivo rat models that are currently available. As an antigen, we used a high molecular mass mucin preparation purified from the spent media of rat tracheal surface epithelial cells in primary culture. Seven monoclonal hybridomas were obtained, among which mAbRT03 showed the highest immunoreactivity against the mucin. All of the antibodies secreted by these hybridomas recognized carbohydrate epitopes but not sialic acid residues, since their immunoreactivity was completely abolished by treatment of the mucin with 20 mM periodate but not with neuraminidase. Further characterization of mAbRT03 showed that (1) it belongs to the IgM type, (2) it binds to high molecular mass mucins based on Western blot, (3) it could indirectly immunoprecipitate rat airway mucin--and, as we know, this is the first demonstration of immunoprecipitation of airway mucin with anti-mucin antibodies--(4) it binds to the luminal side of tracheal epithelium as well as some goblet cells based on immunohistochemistry, and (5) it also recognizes in vivo airway mucins from rats, but not from human nor hamsters, which have been purified from the airway lavage fluids. This is the first monoclonal antibody against rat airway mucin, which has been developed against purified rat airway mucins. Therefore, mAbRT03 should be able to serve as an invaluable tool in studying the regulation of airway mucins using various intact rat models that are currently available.     

Anaesthesia and the broken hearted. 170th annual oration: Royal Victoria Hospital, Belfast 2nd October 1997

Endoscopic evaluation of the patient with lung metastases takes on many forms depending upon the extent of disease and the intent of treatment, be that curative or palliative. Thorascopy, and occasionally mediastinoscopy, may be helpful in assessing operability in patients with extensive disease on a preoperative computed tomography scan. However, when in doubt, exploration is always indicated in the young, good risk patient. Palliative efforts usually concern airway obstruction and malignant effects. A variety of technologies, including laser, brachytherapy, and endoluminal stents, helps manage symptomatic bronchial or tracheal lesions.     

Pulmonary airway resistance with the endotracheal tube versus laryngeal mask airway in paralyzed anesthetized adult patients

BACKGROUND: The hypothesis that airway resistance is less with the laryngeal mask airway than with the endotracheal tube was tested. METHODS: Thirty-six paralyzed, anesthetized adult patients with no respiratory disease (American Society of Anesthesiologists physical status 1-3; age, 18-80 yr) were randomly allocated (9 men, 9 women in each group) to receive either a size-4 laryngeal mask airway or an endotracheal tube (men, 9-mm ID; women, 8-mm ID). A pulmonary monitor with flow transducer and esophageal balloon was used to measure peak airway pressure and mean airway resistance (device resistance plus pulmonary airway resistance) at three different tidal volumes (5, 10, and 15 ml/kg). Device resistance was measured in vitro with the distal end of the endotracheal tube or laryngeal mask airway open to the atmosphere and using the same ventilator settings. Pulmonary airway resistance was derived by subtracting the mean device resistance from the mean airway resistance. RESULTS: Peak airway pressure, mean airway resistance, device resistance, and pulmonary airway resistance were greater for the endotracheal tube (all P < 0.0001). CONCLUSIONS: The laryngeal mask airway triggers less bronchoconstriction than does the endotracheal tube in paralyzed anesthetized adult patients. This may have implications for maintaining intraoperative pulmonary function and reducing the risk for atelectasis and pulmonary infection.     

A comparison of the nasal mask and the nasopharyngeal airway in paediatric chair dental anaesthesia

This study compared the quality of anaesthesia and surgical access afforded by two techniques for the administration of anaesthesia during paediatric chair dental procedures. A total of 50 ASA 1 paediatric day case patients were randomly assigned to receive anaesthesia through either the traditional Goldman nasal mask or through a nasopharyngeal airway. Patients in the nasal mask group were judged to have significantly worse airway patency (p = 0.0001) and significantly more episodes of airway obstruction (14 vs. 4; p = 0.0032) than those in the nasopharyngeal airway group. Anaesthetic, surgical and oxygen saturation data did not differ significantly between the two groups. Operating conditions were universally graded as excellent in the nasopharyngeal airway group, while those in the nasal mask group were graded as excellent/good in only 79% of cases (p < 0.0001). These results suggest that better quality anaesthesia and operating conditions can be achieved by using a nasopharyngeal airway rather than the traditional nasal mask for the administration of anaesthesia to paediatric chair dental patients.     

Thermoregulatory responses of mesic and xeric rodent species to photoperiod manipulations

PURPOSE: To evaluate hypertrophied bronchial arteries on thin-section computed tomographic (CT) scans in patients with bronchiectasis by using CT angiographic correlation. MATERIALS AND METHODS: Spiral CT angiography was performed prospectively in 14 patients (eight men, six women; age range, 34-71 years) with bronchiectasis who were suspected of having bronchial arterial hypertrophy at thin-section CT (performed without contrast medium). The inclusion criteria were tubular (in six patients) or nodular (in 14 patients) areas of soft-tissue attenuation that had an appearance unlike that of lymph nodes at thin-section CT and that were within the mediastinum and around the central airway. These findings were subsequently correlated with the spiral CT angiographic findings. RESULTS: At comparative analysis of thin-section CT scans and CT angiograms, seven of the eight (88%) tubular lesions and 19 of the 36 (53%) nodular lesions in the mediastinal soft tissue were proved to be hypertrophied bronchial arteries. All of the six (100%) tubular and 19 of the 21 (90%) nodular lesions around the walls of the main (primary) and lobar bronchi were hypertrophied bronchial arteries. In eight (57%) patients, CT angiograms showed 11 intraluminal protrusions caused by hypertrophied bronchial arteries in the main bronchi, lobar bronchi, or both. CONCLUSION: Nodular and tubular structures in the mediastinum and around the central airway on thin-section CT scans in the patients with bronchiectasis are suggestive of hypertrophied bronchial arteries. Recognition of the hypertrophied bronchial artery can be critical for the bronchoscopist.     

Pathogenesis of leukocytoclastic vasculitis

A prospective protocol for the management of the airway was applied to patients in the ICU. Acute complications due to intubation and tracheotomy as well as laryngo-tracheal lesions were studied in 125 consecutive patients during one year from the moment of extubation. Thirty four cases (27%) needed reintubation, and 58 tracheotomies were performed (46%). The average length of intubation was of 10 +/- 7 days. Sixty five patients (53%) had acute complications due to intubation and 30 (52%) had acute complications due to the traccotomy. The high incidence of laryngo-tracheal lesions in the 85 patients who underwent early exploration (76 cases [90%]) was reduced in those who underwent late exploration (11 cases [20%]). Analysis of possible prognostic factors in the development of late lesions allows us to affirm that a reduction in the length of intubation diminishes the presence of late lesions. We recommend the avoidance of oro-tracheal intubation prolonged for more than 10 days by the early carrying out of tracheotomy.     

Role of viscoelasticity in the tube model of airway reopening. II. Non-Newtonian gels and airway simulation

The influence of viscoelastic gels as lining fluids on the pressure-velocity relationships in an airway tube model (Gaver et al. J. Appl. Physiol. 69: 74-85, 1990) was examined. A flow instability was observed due to the occurrence of a sol-gel transition in the viscoelastic properties under flow conditions. We further report measurements of the viscoelastic properties of airway secretions. Airway secretions are gels under small strains and have a yield stress of 4-7 dyn/cm2. Secretions from the pharyngeal airway show lower elasticity than secretions from the trachea. The airway reopening process is simulated using a Weibel lung geometry by incorporating the constitutive equations from the model gel studies and utilizing the rheological data on airway secretions. In these simulations, a "popping-open" phenomenon arises from a flow instability in airway generations 8-14 when the rheological properties of the lining fluids are assumed to be similar to those of pharyngeal secretions. On the basis of these studies, the elasticity of airway secretions plays an important role in airway reopening.     

Comparison of active and passive manoeuvres on the pattern of airway closure in man

The effect of active and passive manoeuvres on closing volume was studied in conscious subjects. There were no significant differences in closing volume in nine of 10 non-smokers. There was a significantly greater closing volume with the passive manoeuvre (airway pressure +3 kPa to --2 kPa) in seven of nine smokers and one non-smoker with evidence of mild obstructive airway disease. The sensitivity of the closing volume to airway pressure could not be reproduced in three non-smokers exposed to a histamine aerosol. In two of three smokers the effect of airway pressure on closing volume was abolished by salbutamol. The results suggest that subjects with irritable airways may show an increase in closing volume with a change in airway pressure.     

Time-course of antigen-induced airway inflammation in the guinea-pig and its relationship to airway hyperresponsiveness

The causative relationship between airway inflammation and hyperreactivity is unclear, since inflammatory changes have been examined at one or, at most, a few time-points after antigen challenge in both human asthma and animal models. We have made a detailed investigation of inflammatory and functional changes in the airways up to 8 days after antigen challenge in guinea-pigs. In particular, we examined the hypothesis that eosinophil-derived mediators contribute to tissue damage and the development of airway hyperresponsiveness. Following antigen challenge, the influx of inflammatory cells and mediator release in airway tissue and bronchoalveolar lavage fluid were correlated temporally with histopathological changes in airway tissue and airway responsiveness. Eosinophil influx was demonstrable at 4 h. Eosinophilia peaked after 24 h and persisted for at least 8 days. Parallel increases in the concentrations of major basic protein and eosinophil cationic protein in bronchoalveolar lavage fluid indicated that the eosinophils were activated. Eosinophilia was accompanied by subepithelial oedema and epithelial damage co-localized with major basic protein immunoreactivity. A transient neutrophilia (< 48 h duration) and an increase in neutrophil elastase in bronchoalveolar lavage fluid peaked at 14 h. The proportion of airway macrophages with an activated morphology increased at 8 h and remained markedly elevated until 72 h. Airways were hyperresponsive to histamine at 4 h and for at least 8 days. The antigen-induced airway inflammation resemble in time-course and histopathology that seen in antigen-challenged asthmatics, and indicate that the eosinophil and its cytotoxic proteins may be major mediators of airway mucosal damage and airway hyperresponsiveness.     

GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice

The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-CSF can initiate a Th2-driven, eosinophilic inflammation in the airways. On day -1, Balb/c mice were infected intranasally with an adenovirus construct expressing GM-CSF (Ad/GM-CSF). From day 0 to day 9 mice were exposed daily to an OVA aerosol. Mice exposed to OVA alone did not show any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterized by eosinophilia and goblet cell hyperplasia. Migration of eosinophils into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 and class II MHC were critically required to generate airway eosinophilia. After resolution, airway eosinophilia was reconstituted after a single OVA exposure. Flow cytometric analysis of dispersed lung cells revealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T cells in mice exposed to OVA and Ad/GM-CSF. Our data indicate that expression of GM-CSF in the airway compartment increases local antigen presentation capacity, and concomitantly facilitates the development of an antigen-specific, eosinophilic inflammatory response to an otherwise innocuous antigen.     

Value of rigid bronchoscopy and cytodiagnosis of bronchial washings in detecting bronchial carcinoma in the presence of a carcinoma of the upper aerodigestive tract

Respiratory viral infections have been associated with exacerbations of asthma in humans, and are known to produce airway obstruction and hyperresponsiveness in rats. Virus-induced airway dysfunction may result in part from inflammatory cells and their products, and agents that target these mechanisms might therefore attenuate viral airway injury. The 21-aminosteroid class of drugs has been reported to attenuate tissue injury in a variety of models, and we hypothesized that U-83836E, an orally-active aminosteroid, would prevent the development of airway dysfunction during acute viral illness. Adult rats were inoculated with either parainfluenza type 1 (Sendai) virus or sterile vehicle, treated with either U-83836E 20 mg/kg or water by oral gavage twice daily, and studied on postinoculation day 5, 6 or 7. Anesthetized, paralysed, mechanically ventilated rats were placed in a body plethysmograph for measurements of airway obstruction (resistance, dynamic compliance, eucapneic PaO2), and responsiveness to i.v. methacholine; lungs were lavaged to obtain inflammatory cells. The water-treated virus group was significantly different from the non-infected controls for all variables. Virus-induced hyperresponsiveness was attenuated (P = 0.027) by aminosteroid treatment, although airway obstruction and inflammation were not improved by the treatment. We conclude that 21-aminosteroids may protect airways from virus-induced hyperresponsiveness.     

Efficacy of transbronchial biopsy in pulmonary vaculitides

This study was performed to determine the value of transbronchial biopsy (TBB) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and mild-to-moderate pulmonary involvement. Included in the study were 19 patients with Wegener's granulomatosis (WG) and six patients with Churg-Strauss syndrome (CSS) with evidence of active pulmonary disease but without gross parenchymal lesions accessible by radiologically guided biopsy. All of the patients had undergone staging examinations which included TBB taken from peripheral lung tissue and from any focal tracheobronchial lesions. Any suspicious lesion in the upper respiratory tract was biopsied by an otolaryngologist and the number of positive biopsies was compared with that of TBB. In the WG patients, only two out of 17 biopsies of alveolar tissue yielded histopathological findings supporting the diagnosis of WG. In five WG patients, ulcerative or exophytic airway lesions were found whose histopathologies were invariably positive. Otolaryngological examination revealed abnormal findings in 19 WG patients and biopsies from these sites yielded positive results in 13 instances. In CSS, TBB produced a diagnostically helpful histopathology in four of six cases and biopsies from the upper respiratory tract were positive in five out of six cases. We conclude that transbronchial biopsies of alveolar tissue are seldom positive in Wegener's granulomatosis patients with mild-to-moderate pulmonary disease unless they are taken from grossly abnormal lung areas. Conversely, ulcerative, exophytic or stenotic tracheobronchial lesions had a high rate of positive findings. These results further suggest that the upper rather than the lower respiratory tract should be the biopsy site of first choice in Wegener's granulomatosis. In Churg-Strauss syndrome, the upper and lower respiratory tract seem to yield a roughly equal number of positive biopsies.