Effects of heat and moisture exchangers on tracheal mucociliary clearance in laryngectomized patients: a multi-center case-control study.

After total laryngectomy, inspired air is no longer optimally conditioned by the upper airways. Impaired mucociliary clearance and histological changes of respiratory epithelium, such as loss of ciliated cells, have been described in laryngectomized patients. Heat and moisture exchangers (HMEs) are passive humidifiers that re-condition the inspired air. Aim of this study was to assess the effect of HMEs on tracheal epithelium and tracheal mucus transport velocity (TMV). Tracheal brush biopsies were collected in three groups of TLE patients: 21 long-term HME users, 10 non-HME users, and 16 non-HME users before and after 4-9 months HME use. Tracheal epithelium biopsies were assessed using a digital high-speed camera mounted onto a light microscope. TMV was determined by scintigraphy in the first two patient groups. Significantly more ciliated cells were found in HME users compared to non-HME users (p = 0.05). TMV was higher in HME users (median 2 mm/min; 0-7.9) compared to non-HME users (median 0.8 mm/min; 0-12.3), but this difference was not significant (p = 0.37). One-hour breathing without HME in long-term HME users did not measurably decrease TMV (p = 0.13). The long-term use of an HME restores/prevents the loss of tracheal ciliated cells. A significant improvement in TMV was not found. Short-term (one hour) detachment of an HME has no measurable effect on TMV.

Respiratory epithelial adenomatoid hamartoma in the nasopharynx.

We present a case report of a female patient with complaints of single-sided nasal obstruction. A polypoid structure was seen in the nasopharynx. Histologic examination showed a respiratory epithelial adenomatoid hamartoma -- a rare, benign lesion. Therapy consisted of complete excision. In line with previous reports, the lesion did not recur during 13 months of follow up. The clinical and pathological features of this abnormality are discussed.

Measuring plasma exudation in nasal lavage fluid and in induced sputum as a tool for studying respiratory tract inflammation.

We performed nasal lavage (NAL) combined with induced sputum to determine exudative inflammation in the upper and lower airways in patients with chronic sinusitis and in controls. To monitor plasma exudation into the respiratory lumen and loss of size-selectivity of the mucosa, we determined the sample-to-serum ratio of albumin and alpha-2-macroglobulin, Qa1b and Qa2m, and the dilution independent Relative Coefficient of Excretion, RCE=Qa2m/Qa1b. To detect low protein levels in NAL and induced sputum we adapted an ELISA system for alpha-2-macroglobulin described by Out et al. [Clin. Chim. Acta, 165 (1987) 277-288], and modified this into a sensitive ELISA for albumin. Dithiothreitol, added to increase sputum solubility, did not interfere with the analysis, nor did N-ethylmaleimide, added to block dithiothreitol. In this study plasma exudation in induced sputum is significantly increased in patients with chronic sinusitis, compared to controls. Plasma exudation in NAL is also increased in patients, although not significant. The RCE in NAL and sputum is well-correlated in one of the three study visits. There is much variation in sample protein-levels partly due to differences in dilution and the heterogeneity of the studied population. Determination of plasma exudation together with RCE in NAL and induced sputum is a good, non-invasive way to quantify inflammation of airway mucosa.

Early and late allergic reaction in the nose assessed by whole body plethysmography.

Physiological changes during late phase nasal responses after allergen challenge are difficult to establish and different criteria are used for the definition of a positive late phase nasal reaction. The objective of this study was to assess the value of whole body plethysmography in detecting changes in nasal airway resistance after allergen challenge and to suggest criteria for the definition of early and late phase nasal reactions. Nasal challenge with allergen was performed in 15 allergic patients. Nasal resistance was followed until 10 h after allergen challenge and on a control day using whole body plethysmography. The mean percentage changes in the inspiratory nasal resistance during the early phase period (0.25-2 h) and the late phase period (4-10 h) were significantly higher on the allergen challenge day than on the control day (p=0.001 and p=0.01, respectively). The mean percentage change in the inspiratory nasal resistance during the early and late phase period on the control day plus 2 times the standard deviation served as cut-off point for a positive reaction. Using this definition, all patients had early reactions and 7 of the 15 patients (47%) also had late reactions. We conclude that whole body plethysmography is a useful, noninvasive method for the measurement of the physiological changes in the nose following allergen challenge.

Albumin and immunoglobulin levels in nasal secretions of patients with nasal polyps treated with endoscopic sinus surgery and topical corticosteroids.

BACKGROUND: Nasal polyposis is principally treated by surgery, which may be combined with administration of topical corticosteroids to postpone or prevent recurrences. OBJECTIVE: In this study endoscopic sinus surgery and subsequent use of topical corticosteroids (budesonide) for 1 year was evaluated. METHODS: Clinical data of 41 patients with nasal polyps were evaluated, and their nasal secretions were compared with those of 26 healthy persons (control subjects). RESULTS: The patients had much higher initial total protein, albumin, IgM, secretory IgA (S-IgA) (p < 0.001 for all), and IgG concentrations (p < 0.05) than the control subjects. Treatment resulted in a significant decrease of S-IgA (p < 0.001) within 6 months. IgM and IgG concentrations decreased more slowly (p < 0.001 and p < 0.05 at 1 year, respectively). IgE levels decreased, but we could not demonstrate significance. Relative to total protein levels, the albumin and S-IgA levels decreased within 6 months (p < 0.005 and p < 0.001, respectively). The excretion of all proteins remained higher in patients than in the control subjects, even after 1 year of topical corticosteroid treatment. Clinical evaluation showed slightly higher S-IgA levels in patients with an IgE-mediated allergy than in those without such a condition, and the recurrence rate was highest in the former group (75% vs 48%). CONCLUSION: The data support the hypothesis that inflammatory reactions in the nasal mucosa play a role in the pathogenesis of nasal polyps but also suggest an additional causative factor.

Localization and morphology of antigen-presenting cells in the adenoid of children with otitis media with effusion.

This study describes the localization of antigen-presenting cells (APC) in the different compartments in adenoids of children with otitis media with effusion (OME) and "healthy" children and adults. It is shown that the adenoid of children with OME contains a relatively high number of OKT6 and RFD1 positive cells. Moreover, accumulations of these cells are present in the extrafollicular areas of these adenoids. Very occasionally dendritic cells in the epithelial microenvironment contain Birbeck granules, indicating characteristic Langerhans cells. These OKT6 positive cells are not seen in the adenoids of the control group. Our results clearly show a relation between the presence of dendritic cells and the occurrence of OME. No differences are seen in localization and morphology of the APC in the studied adenoids.

[Correction of the external ear using cartilage-sparing techniques]. / Oorschelpcorrectie met kraakbeensparende technieken.

OBJECTIVE: To establish the value of cartilage sparing suture techniques for correction of prominent ears. DESIGN: Retrospective study. LOCATION: Gooi-Noord Hospital, Blaricum, the Netherlands. METHOD: Between 1989 and 1992, 117 ears in 62 patients were corrected for prominence. Results were evaluated using the McDowell criteria for anatomy and localisation of the ear. RESULTS: Of 117 ears 108 were corrected successfully. A recurrence was seen in 6 ears and 3 ears showed overcorrection. Reoperation was needed in 2 ears. A suture was extruded in 15 ears, which could be treated relatively easily in 14. CONCLUSION: Cartilage sparing suture techniques for correction of the specific anatomic deformities of prominent ears prove to be successful. Suture extrusion was the most frequent, but minor, complication. Suture extrusion appears to be dependent upon suture material and localisation.

Defects in cellular immunity in chronic upper airway infections are associated with immunosuppressive retroviral p15E-like proteins.

Partial defects in cell-mediated immunity have been shown in patients with chronic purulent rhinosinusitis. These defects, ie, impaired delayed-type hypersensitivity (type IV) skin reactions on commensal microorganisms of the upper respiratory tract and impaired chemotactic responsiveness of monocytes, are associated with the presence of immunosuppressive retroviral p15E-like proteins in the serum of these patients. In this study, we tested whether partial defects in cellular immunity could also be demonstrated in other groups of patients with chronic upper airway infections. Therefore, three well-characterized groups of patients with chronic upper airway infections were investigated: (1) patients with primary ciliary dyskinesia, a congenital disorder of respiratory cilia, resulting in absence of mucociliary clearance and, as a consequence, in chronic respiratory infections; (2) patients with chronic rhinosinusitis, with normally functioning cilia and with nasal polyps; and (3) patients with chronic rhinosinusitis, with normally functioning cilia but without nasal polyps. Our results show that in all three groups, most patients (87%) had defects in cellular immunity associated with the presence of p15E-like proteins in their serum. These results indicate that during chronic infections of the upper respiratory tract, immunosuppressive retroviral p15E-like proteins are found, which are probably responsible for the partial immune defects found in these patients.

Eosinophils in nasal polyps and nasal mucosa: an immunohistochemical study.

Immunohistochemical staining was performed at the time of endoscopic sinus surgery (ESS), after 6 months, and after 1 year on nasal polyps and biopsy specimens of the macroscopically unaffected mucosa of the middle and inferior turbinate bones of 46 patients with nasal polyps. During the follow-up period the patients were treated with topical corticosteroids. At time of ESS significantly more BMK13+ and EG1+ (pan eosinophil markers) and EG2+ (activation marker) eosinophils were found in the polyps than in the macroscopically unaffected mucosa of the middle and inferior turbinate bones of the patients. In the middle and inferior turbinate bones of 10 healthy subjects no EG2+ (activated) eosinophils were detected, whereas low-to-moderate numbers of BMK13+ and EG1+ eosinophils were seen in these specimens. This emphasizes that eosinophils play a role in the pathogenesis of nasal polyps. Compared with numbers at ESS, after 6 months and 1 year of follow-up, lower numbers of BMK13+, EG1+, and especially of EG2+ eosinophils were found in recurrences of polyps and in the macroscopically unaffected mucosa of the middle and inferior turbinate bones of the patients. The decrease in number of EG2+ (activated) eosinophils is an indication of a reduced local inflammatory reaction, and could be an important factor in postponement of recurrences of nasal polyps.

Distribution of retroviral p15E-related proteins in neoplastic and non-neoplastic human tissues, and their role in the regulation of the immune response.

In patients with head and neck carcinomas and in patients with chronic purulent upper airway infections, low molecular weight retroviral p15E-like factors are found. These factors are responsible for partial defects in the cellular immune response. We studied the distribution of these p15E-related proteins in neoplastic, inflamed and normal human tissues and related these findings with the presence of p15E-like factors in patients' sera. Demonstration of p15E-like proteins in sera of patients with upper airway infections and of patients with head and neck carcinomas correlated exclusively with the presence of p15E in normal and pathologic epithelium of the upper respiratory tract. p15E was not demonstrated in epithelia of other localizations. Our results suggest that chronic stimulation or neoplastic transformation of the epithelia of the upper respiratory tract stimulates the production of p15E-like proteins leading to their reported immunosuppressive actions.

Isolation and characterization of dendritic cells from adenoids of children with otitis media with effusion.

Dendritic cells were enriched from adenoids of children with otitis media with effusion (OME) by density gradient centrifugation and culture techniques. An enrichment of 40-140-fold was obtained for dendritic cells. These cells were identified using morphology, enzyme cytochemistry, immunocytochemistry and functional criteria. Dendritic cells could be easily distinguished from macrophages. It appeared that the MoAb EBM11 (CD68) discriminated between dendritic cells and macrophages; in dendritic cells this activity was localized in a spot, whereas in macrophages it was found throughout the whole cytoplasm. The fractions enriched with dendritic cells showed a strong stimulatory effect on allogeneic T cells. These responses were MHC class II dependent since they could be blocked by anti-HLA-DR/DQ MoAbs. The data clearly show that dendritic cells from adenoids of children with OME still have functional capacities.

Endoscopic treatment of pharyngeal pouches: electrocoagulation vs carbon dioxide (CO2) laser.

Endoscopic treatment of a hypopharyngeal diverticulum was performed in 75 patients during the period 1976-1990. Initially electrocoagulation was used to divide the septum between the diverticulum and oesophagus. More recently, the CO2 laser combined with the operating microscope has been used. Although this has reduced the need for multiple endoscopic procedures compared to the electrocoagulation technique, this reduction was not statistically significant. In our follow-up group of patients, 49 (72.7%) were highly satisfied and 14 (19.6%) fairly satisfied. In this respect no significant differences between the electrocoagulation and laser group were found. Although we consider the use of the CO2 laser and operating microscope as a technical improvement of the former Dohlman procedure, further assessment needs to be done to evaluate whether laser therapy does offer an improvement in results.

Clinical aspects and distribution of immunologically active cells in the nasal mucosa of patients with nasal polyps after endoscopic sinus surgery and treatment with topical corticosteroids.

Clinical parameters of 72 patients who were operated upon for nasal polyps were evaluated as well as biopsy specimens of the mucosa of the middle and inferior turbinates of 41 of these patients. Biopsies were taken at the time of endoscopic sinus surgery (ESS), after 6 months and after 1 year in 23 patients. During the follow-up period the patients were treated with topical corticosteroids (budesonide). At the time of ESS significantly more CD8+ (suppressor/cytotoxic) cells than CD4+ (helper/inducer) cells were found in the middle and inferior turbinates. At 6 months significantly more CD4+ cells were found than at the time of ESS, whereas at 1 year the number of CD4+ cells had decreased and was lower than at 6 months. These data support the theory that the occurrence of nasal polyps is associated with T-cell-dependent disturbances. Clinical evaluation revealed that most of the patients with chronic airway obstruction had better pulmonary functions postoperatively or required less medication for lung disease. These findings show that ESS combined with topical corticosteroids has a positive effect on upper and lower respiratory tract pathology.

Immunoglobulin concentrations in nasal secretions differ between patients with an IgE-mediated rhinopathy and a non-IgE-mediated rhinopathy.

Nasal secretions from patients with an IgE-mediated rhinopathy, patients with a non-IgE-mediated rhinopathy, and healthy control subjects were collected with a newly developed direct aspiration system. Total protein, albumin, secretory IgA (sIgA), IgE, IgG, and IgM concentrations were measured in the nasal secretions to detect whether the nasal pathology is reflected in nasal secretion protein concentrations. It was found that protein and immunoglobulin concentrations in nasal secretions were inversely related to amount of secretion in the nasal cavity. Both patients' groups had a significantly higher sIgA to protein ratio than the healthy control subjects. Furthermore, patients with an IgE-mediated rhinopathy had significantly higher sIgA and IgM to total protein ratios in their nasal secretions than patients with a non-IgE-mediated rhinopathy. Probably these differences are due to changes in immunoregulation.

Primary ciliary dyskinesia and the middle ear.

The middle ear cavity and the eustachian tube contain a well-functioning mucociliary clearance system. To learn more about the importance of this mucociliary clearance, we studied patients with primary ciliary dyskinesia, in whom mucociliary clearance is absent. Thirty-six patients were investigated by means of a questionnaire; in 16 of these patients, otological and audiological studies could be performed. In patients with primary ciliary dyskinesia, a discrepancy was found between subjective ear complaints and the actual middle ear function. Moreover, it appeared that for the middle ear system, mucociliary clearance is of importance only in the first 3 decades of life. With aging, however, a deficient mucociliary clearance system in the middle ear and eustachian tube can be fully compensated for.

Function and morphology of respiratory cilia in situs inversus.

The activity and ultrastructure of respiratory cilia were studied in 13 individuals with situs inversus but without serious respiratory complaints, in 8 patients with Kartagener's syndrome and in 50 healthy controls without situs inversus. In 3 individuals with situs inversus abnormal ciliary activity was found, comparable in every aspect to the ciliary activity in patients with Kartagener's syndrome. In 4 individuals with situs inversus a dynein arm deficiency was present in the cilia, with abnormal ciliary activity in 3 of them. The number of outer dynein arms per cilium differed significantly between the 3 groups (P less than 0.02). Apparently, situs inversus without serious respiratory complaints can be associated with primary ciliary dyskinesia. Based on the findings in this study, the incidence of primary ciliary dyskinesia in the Caucasian population appears to be 1:12,500.

Nasal secretions from patients with polyps and healthy individuals, collected with a new aspiration system: evaluation of total protein and immunoglobulin concentrations.

This study was designed, first, to test a new system for aspiration of human nasal secretions and, secondly, to evaluate protein and immunoglobulin concentrations in these secretions at different levels of secretory activity. The direct aspiration system combines the advantages of minimal irritation of the nasal mucosa with the facility to determine concentrations per gram of secretion. The total protein and immunoglobulin concentrations were inversely related to the amount of secretion obtained. Variations in fluid secretion throughout the day may be responsible for this relationship. The inverse relationship was much more significant in patients with nasal polyps, in which much higher concentrations were found, than in healthy subjects. Ratios of immunoglobulin to total protein were independent of the amount of secretion obtained. Compared to the controls, the ratios of IgM and IgG to protein in the secretions of the patients were significantly increased. The secretory immunoglobulin A to total protein ratios were only slightly higher in the patients' secretions.

Adhesion receptors involved in clustering of blood dendritic cells and T lymphocytes.

The relationship of dendritic cells (DC) isolated from the peripheral blood to those of lymphoid tissue is, in terms of maturation and function, incompletely understood. In our present study, we have explored the molecular basis of adhesion of T cells to blood DC. Analysis of the expression of adhesion receptors on the cell surface of blood DC revealed that these cells express lymphocyte function-associated antigen (LFA)-1 (CD11a/18), ICAM-1 (CD54), LFA-3 (CD58) and CD44, but are very late antigen (VLA)-4 (CD49d) and vascular cell-adhesion molecule (VCAM)-1 negative. The LFA-1 pathway was found to play a key role in T cells-blood DC adhesion; monoclonal antibodies (mAb) against both LFA-1 and ICAM-1 strongly inhibited adhesion between those cells. Moreover, a T cell clone from an LFA-1-deficient patient showed poor binding to blood DC. The important role of LFA-1 in T cell-blood DC adhesion was also supported by the metabolic energy and divalent cation dependence of the interaction. mAb against LFA-3 and CD2 did not inhibit T cell-blood DC binding. In contrast to the strong inhibition by antibodies to LFA-1 and ICAM-1, antibodies to CD44 enhanced conjugate formation between T cells and blood DC. Together, our results show that the LFA-1/ICAM-1 pathway plays a central role in T cell-blood DC adhesion, a situation like that in T cell adhesion to lymphoid DC. However, unlike lymphoid DC, blood DC do not express VCAM-1 nor use LFA-3 for T cell binding.

Lymphocytes and nonlymphoid cells in human nasal polyps.

Immunohistochemical stainings were performed on polyp specimens of 48 patients and on mucosal biopsy specimens of the middle and inferior turbinates of 23 and 28 patients, respectively. Significantly more CD8+ (suppressor/cytotoxic) than CD4+ (helper/inducer) cells were found in the polyps. The number of CD2+, CD4+, and CD8+ lymphocytes in nasal polyps were very similar to the number in the macroscopically unaffected mucosa of the middle turbinates, whereas scores in the inferior turbinates were lower. In healthy subjects, the differences were smaller. CD22+ B cells were detected in varying numbers in the polyps in more or less organized clusters. Significantly more HLA-DR+ cells were found in polyps and middle turbinates than in the inferior turbinates. Eosinophils were found in moderate to large numbers in polyps of 77% of the patients. Mast cells and plasma cells were detected in moderate numbers, whereas neutrophils were found in 35% of the patients. In the middle and inferior turbinates varying but small numbers of eosinophils, mast cells, plasma cells, and neutrophils were found. In considering these findings, the role of chronic inflammation with T cell-dependent disturbances is discussed with regard to the pathogenesis of nasal polyps.