Burden of allergic rhinitis and impact of MP-AzeFlu from the patient perspective: pan European patient survey.

OBJECTIVE: The aims of this survey were to (1) assess the burden of allergic rhinitis (AR) from the patient perspective, (2) investigate MP-AzeFlu use in real life and its impact on patients' lives and (3) explore factors associated with treatment satisfaction. METHODS: A cross-sectional, quantitative, online, questionnaire-based survey was conducted in seven European countries (March-June 2019). Questions explored AR burden and treatment satisfaction. Satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication 9-item (TSQM-9; max score = 100). Participants (aged ≥18 years) had a doctor/healthcare provider confirmed AR diagnosis and used MP-AzeFlu within the last year. RESULTS: Pre-MP-AzeFlu treatment, participants (n = 1004) reported an average of 3.3 (SD:3.5) doctor visits/year, 8.1 (SD:11.0) days/year absenteeism and 15.8 (SD:18.9) days/year presenteeism due to AR. Only 48% of participants used MP-AzeFlu twice/day as recommended. Post-MP-AzeFlu 57% of participants reported better QoL, 47% reported fewer doctor visits and 52% discontinued polypharmacy. Absenteeism and presenteeism were reduced by 2.5 (SD 10.0) and 7.3 (SD:16.0) days/year, respectively. 70% of participants were more/much more satisfied with MP-AzeFlu versus previous AR treatment(s), and ≥70% were satisfied/extremely satisfied with its ability to prevent/treat AR, relieve symptoms and with its onset of action. Mean global, effectiveness and convenience TSQM-9 scores were 70.0 (SD:19.8), 68.3 (SD:21.6) and 72.7 (SD:20.4), respectively. Treatment satisfaction and effectiveness were significantly improved when MP-AzeFlu was taken as recommended. CONCLUSIONS: The impact of AR on patients' lives remains high. Real-life use of MP-AzeFlu reduces that impact and is associated with a high level of effectiveness, convenience and global satisfaction.

Intralymphatic Immunotherapy: Update and Unmet Needs.

Allergen-specific immunotherapy (AIT) is the only allergy treatment that confers long-term symptom amelioration for patients suffering from allergy. The most frequently used allergen application route is subcutaneous injection (SCIT), commonly taken as the gold standard, followed by sublingual (SLIT) or oral (OIT) application of allergen preparations. This is an up-to-date review of the clinical evidence for a novel route of allergen application, i.e., directly into lymph nodes - intralymphatic immunotherapy (ILIT). The major advantages of ILIT over the current AIT approaches are its short duration and the low allergen doses administered. The whole treatment consists of merely 3 ultrasound-guided injections into inguinal lymph nodes 1 month apart. While the number of patients included in randomised controlled trials is still limited, the clinical results for ILIT are encouraging, but more clinical trials are needed, as well as more preclinical work for optimising formulations.

A multicenter, prospective, noninterventional study in a Norwegian cohort of patients with moderate-to-severe allergic rhinitis treated with MP-AzeFlu.

BACKGROUND: Allergic Rhinitis and its Impact on Asthma guidelines recently recommended a treatment strategy for allergic rhinitis (AR) based on disease control rather than symptom severity by using a visual analog scale (VAS) to categorize control. OBJECTIVES: To evaluate the effectiveness of MP-AzeFlu (Dymista®) by using this VAS in routine clinical practice in Norway. MP-AzeFlu comprises a novel formulation that contains azelastine hydrochloride, fluticasone propionate and excipients delivered in a single spray. METHODS: This multicenter, prospective, noninterventional study enrolled patients (n = 160) with moderate-to-severe AR and acute symptoms who were eligible to receive treatment with MP-AzeFlu according to its summary of product characteristics. Patients assessed symptom severity by using a VAS from 0 (not at all bothersome) to 100 mm (very bothersome) in the morning before MP-AzeFlu use on days 0, 1, 3, 7, and after ∼14 days. On day 3, the patients assessed their level of disease control as well controlled, partly controlled, or uncontrolled. The proportion of Norwegian patients who achieved defined VAS score cutoffs for "well-controlled" and "partly controlled" AR were also calculated. RESULTS: MP-AzeFlu reduced the mean ± standard deviation VAS score from 68.1 ± 16.4 mm at baseline to 37.4 ± 25.9 mm on the last day, a reduction of 30.8 ± 27.2 mm. The results were consistent, irrespective of disease severity, phenotype (i.e., seasonal AR [SAR], perennial AR [PAR], SAR plus PAR, unknown) or age (i.e., 12-17, 18-65, and >65 years). Of the patients (with recorded data), 88.1% considered their symptoms to be partly or well controlled at day 3; and 19.5, 32.0, 50.0, and 61.0% of the patients achieved a ≤38 mm well-controlled VAS score cutoff on days 1, 3, 7, and the last day, respectively. CONCLUSIONS: MP-AzeFlu provided rapid sustained symptom control in a routine clinical practice in Norway, which provided support for its effectiveness for the treatment of AR in real life.

MP-AzeFlu provides rapid and effective allergic rhinitis control in real life: A pan-European study.

BACKGROUND: The European Union has prioritized allergic rhinitis (AR) control. Contre les Maladies Chronique pour un Vieillissement Actif Allergic Rhinitis and its Impact on Asthma has endorsed the visual analog scale (VAS) as the AR control language and incorporated it into a new AR treatment algorithm. Concurrently, the Respiratory Effectiveness Group and the European Academy of Allergy and Clinical Immunology are striving to improve the quality of published real-life AR research. Our aim was to assess the effectiveness of MP-AzeFlu by using a VAS in a well-designed, real-life, pan-European study. METHODS: A total of 2988 patients (aged ≥ 12 years) with Allergic Rhinitis and its Impact on Asthma defined moderate-to-severe AR from Germany, Sweden, Romania, United Kingdom, Denmark, and Norway were included. Patients (except from the United Kingdom) assessed symptom severity by using a VAS from 0 mm (not at all bothersome) to 100 mm (very bothersome) on days 0, 1, 3, 7, and the last visit (∼day 14) in the morning before MP-AzeFlu use. Patients' perceived level of disease control was assessed on day 3. A VAS score cutoff on day 3 for "well controlled" was determined, and the proportion of patients who achieved this response was calculated. RESULTS: MP-AzeFlu was associated with a mean VAS score reduction from 73.7 mm at baseline to 23.4 mm by the last visit. This reduction was significant (p < 0.001) compared with baseline from day 1 and sustained until the last day of the study. By day 3, 50.3% of patients considered their symptoms well controlled; 18.2, 40.0, 66.6, and 75.9% of the patients achieved the ≤38 mm well-controlled VAS score cutoff on days 1, 3, 7 and the last day, respectively. The results were consistent across countries, age, phenotype, and severity. CONCLUSION: MP-AzeFlu provided effective and rapid symptom control in a real-life pan-European setting and aligned with the European Union, Contre les Maladies Chronique pour un Vieillissement Actif Allergic Rhinitis and its Impact on Asthma, the Respiratory Effectiveness Group, and the European Academy of Allergy and Clinical Immunology objectives, supporting MP-AzeFlu as the drug of choice for the treatment of moderate-to-severe AR.

Rapid recruitment of CD14(+) monocytes in experimentally induced allergic rhinitis in human subjects.

BACKGROUND: Activated TH2 cells and eosinophils are hallmarks of the allergic inflammation seen in patients with allergic rhinitis (AR). However, which cells activate and attract T cells and eosinophils to the inflammatory lesion has not been determined. OBJECTIVE: We wanted to assess the role of mucosal mononuclear phagocytes, consisting of monocytes, macrophages, and dendritic cells, in the local allergic inflammatory reaction. METHODS: Patients with AR and nonatopic control subjects were challenged with pollen extract, and nasal symptoms were recorded. Mucosal biopsy specimens obtained at different time points before and after challenge were used for immunostaining in situ and flow cytometric cell sorting. Sorted mononuclear phagocytes were subjected to RNA extraction and gene expression profiling. RESULTS: In an in vivo model of AR, we found that CD14(+) monocytes were recruited to the nasal mucosa within hours after local allergen challenge, whereas conventional dendritic cells accumulated after several days of continued provocation. Transcriptomic profiling of mucosal mononuclear phagocytes sorted after 1 week of continued allergen challenge showed an activated phenotype at least partially driven by IL-4 signaling, IL-13 signaling, or both. Importantly, gene expression of several TH2-related chemokines was significantly upregulated by the mononuclear phagocyte population concomitant with an increased recruitment of CD4(+) T cells and eosinophils. CONCLUSION: Our findings suggest that the mononuclear phagocyte population is directly involved in the production of proinflammatory chemokines that attract other immune cells. Rapid recruitment of CD14(+) monocytes to the challenged site indicates that these proinflammatory mononuclear phagocytes have a central role in orchestrating local allergic inflammation.

Aspirin desensitization: useful treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) in aspirin-exacerbated respiratory disease (AERD)?

Aspirin intolerance syndrome is due to disturbances in the arachidonic acid metabolism implicating both the lipoxygenase and cyclooxygenase pathways. This results in imbalances of eicosanoid, leukotriene and prostaglandin synthesis. Thus, preinflammatory cysteinyl leukotrienes increase and antiinflammatory prostaglandins (PG) such as PGE2 decrease. Clinically, intolerance reactions to nonsteroidal antiinflammatory drugs (NSAIDs) can lead to different clinical manifestations; five phenotypes of the aspirin intolerance syndrome are listed in the ENDA classification. Aspirin-exacerbated respiratory disease (AERD) is the most common phenotype characterized by an eosinophil-dominated inflammatory disease of the airways that presents clinically with nasal polyps, chronic sinusitis and bronchial asthma. About 34 % of patients with aspirin-induced asthma and rhinosinusitis are thought to have AERD. Important biochemical findings in many AERD patients are increased basal leukotriene levels (at least in cell cultures) that excessively increase after intake of COX-1 inhibitors. Aspirin desensitization uses the repetitive application of aspirin to induce a tolerance to NSAIDs, especially COX-1 inhibitors. After a dose-increase phase reaching a threshold dose, a dose-continuation phase is performed. For application, the nasal, bronchial, oral and intravenous routes have been described. Aspirin desensitization has been proven to be efficacious and safe and was able to reduce the need for other medications in AERD patients.

Bevacizumab in hereditary hemorrhagic telangiectasia-associated epistaxis: effectiveness of an injection protocol based on the vascular anatomy of the nose.

OBJECTIVE/HYPOTHESIS: To evaluate the effectiveness of a standardized intranasal bevacizumab injection in treating hereditary hemorrhagic telangiectasia (HHT)-associated epistaxis. STUDY DESIGN: Prospective pilot study. METHODS: A total dose of 100 mg bevacizumab (25 mg/mL Avastin) was injected submucosally, 50 mg on each side. A total of 0.5 mL was injected in the sphenopalatine area, upper part of bony septum, upper part of the later nasal wall, and the anterior part of nasal floor. No cauterizations or laser therapy were done during or after the procedure. The hemoglobin level and grades of epistaxis were recorded before and monthly after the procedure. The IFT grading system (intensity [I], frequency [F] of epistaxis, and the amount of blood transfusion [T]) and epistaxis severity score (ESS) for hereditary hemorrhagic telangiectasia system were used. Quality of life (QoL) was evaluated before and 4 weeks after the procedure using the Short Form-36 Health Survey questionnaire, Cantril's Self-Anchoring Ladder questionnaire, and Slotosch disease-specific QoL questionnaire. RESULTS: A significant improvement was found in IFT grading (P = .007), ESS grading (P = .001), and hemoglobin level (P = .01). The QoL differences were statistically not significant. CONCLUSIONS: The four-injection site technique of intranasal administration of bevacizumab is an effective treatment option in HHT-associated epistaxis, at least on the short-term effect. Long-term and comparative studies are needed to further evaluate the significance of this treatment modality.

Assay-based response evaluation in head and neck oncology: requirements for better decision making.

This article gives an overview on different current strategies of assay-based response evaluation in head and neck squamous cell carcinomas (HNSCC) and critically summarizes their role and needs for future clinical evaluation. Due to a growing amount of data of phase III clinical trials of multimodality treatment options for HNSCC, treatment planning in regard to optimal outcome is becoming an interdisciplinary challenge. New concepts such as induction chemotherapy with bi- or ternary combinations of chemotherapeutics, integration of targeted therapies, concurrent and sequential chemoradiation concepts, and multimodality-based organ preservation strategies strongly compete with traditional definitive surgical procedures. Moreover, the outcome is difficult to predict due to heterogeneity of a tumor's response, impaired late functional outcome, and increased late toxicity if simultaneously applied to radiation. Retrospectively looking at non-responders with tumors classified as resectable, primary surgery is very likely to have achieved better results, since chemoradiation causes a high degree of early and late toxicities leading to extremely complicated terms and conditions in surgery following current multimodal therapeutic strategies. Unfortunately, predictive information on response characteristics of a given tumor before starting the therapy is not available in daily routine, although heterogeneity in response of a given tumor entity to treatments has been known for decades. Therefore, current therapy strategies for HNSCC still have to ignore this fact, creating an urgent need for the development of proper predictive assays. There are interesting clinical observations showing that response on induction chemotherapy may predict the outcome after radiotherapy. Some trials use this empiric phenomenon to pre-select non-responders for primary surgical treatment avoiding severe salvage complications after failure of complete chemoradiation treatment. Moving one step further, recent literature and our own investigations implicate that response evaluation of the individual patient's HNSCC in a suitable ex vivo assay just before starting the treatment is mature for clinical research. To this end, essential needs and hints are addressed and discussed.

Heterogeneity of epithelial and stromal cells of head and neck squamous cell carcinomas in ex vivo chemoresponse.

BACKGROUND: Valid prediction of the effectiveness of chemotherapeutic agents in individual head and neck squamous cell carcinoma (HNSCC) is desirable and might be achieved using ex vivo assays. METHODS: Three biopsies from each of 15 HNSCC were taken, minced and digested by collagenase. The digested HNSCC was added to serial dilutions of either cisplatin (CIS) or docetaxel (DTX), which were prepared under flavin-protecting conditions in ECM-coated microtiterplates. After 72-h incubation, cultures were methanol-fixed and Giemsa-stained. The cutoff concentration (COC; concentration completely suppressing colony formation) for epithelial cells (EC) and stromal cells (SC) was evaluated. RESULTS: 12/15 HNSCC (80%) were evaluable. Despite significant correlation of COC of CIS in respect of colony formation of EC or SC, no significant differences in response of individual HNSCC specimens were found in the t test for paired samples (p > 0.16). The same applied to DTX. However, EC and SC showed heterogeneity in chemoresponses leading to COC variability of more than one titration step in 44.1% (CIS) and 20% of HNSCC (DTX). No significant correlation between the COC of both cell populations was found in HNSCC specimens. CONCLUSIONS: The ex vivo chemoresponse of EC and SC of HNSCC must be analyzed separately.

Single tissue samples from head and neck squamous cell carcinomas are representative regarding the entire tumor's chemosensitivity to cisplatin and docetaxel.

BACKGROUND: In multimodal therapy concepts for advanced head and neck squamous cell carcinoma (HNSCC), a valid predictive assay for the quick detection of efficient chemotherapeutic agents is desirable. Questionable so far was whether tissue samples of about 100 mg correctly reflect the chemoresponse of a whole HNSCC. This was proven using an ex-vivo colony-forming assay. MATERIALS AND METHODS: Of 14 HNSCC, 3 biopsies each were taken from separate sites, minced, and collagenase digested. HNSCC digests were added to microtiter plates containing serial dilutions of chemotherapeutic agents or medium as control. After 72-h incubation, wells were washed and cultures methanol-fixed before Giemsa-staining. Epithelial colonies were counted. RESULTS: 11/14 HNSCC (78.6%) showed sufficient colony formation allowing reliable cut-off detection. Cut-off concentrations (complete chemotherapeutically suppressed colony formation) between 3.3 microM and >50 microM cisplatin, and 0.55 microM and 17.6 microM docetaxel were detected. Inhibition of colony formation to 50% of colonies detected in controls (IC50) was found between 0.2 microM and 17.9 microM cisplatin or 1.5 microM and 13.7 microM docetaxel. Cut-off concentrations and IC50 of the HNSCC fragments showed a strong correlation (docetaxel: r > 0.80, p < 0.005; cisplatin: r > 0.67, p < 0.044), while being only insignificantly different in the t-test for paired samples (docetaxel: p > 0.163; cisplatin: p > 0.167). CONCLUSION: In most cases, tissue samples of about 100 mg allow a representative assessment of chemoresponse of HNSCC.

Ex vivo responsiveness of head and neck squamous cell carcinoma to vinorelbine.

BACKGROUND: Vinorelbine has been identified as an effective cytostatic drug in head and neck squamous cell carcinoma (HNSCC). To predict the individual chemoresponse, the application of an ex vivo assay to quantify the response of HNSCC to vinorelbine is presented. PATIENTS AND METHODS: Twelve biopsies from primary HNSCC sites and five biopsies from metastatic lesions were analyzed (n = 17). The specimens were investigated ex vivo for the overall, epithelial and stromal chemoresponse to vinorelbine. RESULTS: By selective evaluation of the epithelial chemoresponse, the applied assay identified three specimens as vinorelbine-sensitive (18%), including one de novo sensitivity in a metastatic lesion of a vinorelbine-resistant hypopharyngeal carcinoma. CONCLUSION: Applying flavin-protecting culture methods and with careful correction for the stromal cell effect, the assay generated reliable data for the assessment of the individual chemoresponse of HNSCC specimens to vinorelbine. The assay may, therefore, facilitate the implementation of individualized chemotherapy protocols.

Ex vivo chemosensitivity of head and neck carcinoma to cytostatic drug combinations.

Previous studies focusing on response prediction to chemotherapy by chemosensitivity testing of tumor explants has focused on the response determination of single cytostatic drugs, in contrast to the common clinical application of cytostatic drug combinations. Therefore, the present study was aimed at determining the quantitative ex vivo chemoreactivity of epithelial cells from head and neck squamous cell carcinoma (HNSCC) specimens to cytostatic drug combinations. Specimens from 12 histologically-confirmed HNSCC were investigated. According to a previously established ex vivo colony formation assay, the individual cellular chemoreactivity was determined quantitatively for combinations of 4 cytostatic drugs: cis-platinum (cis-DDP), carboplatin (CBDCA), 5-Fluorouracil (5-FU) and docetaxel (DTX). The tests were performed using drug combinations according to recent clinical therapy regimens in the treatment of solid tumors: i) cis-DDP + 5FU, ii) CBDCA + 5FU, iii) cis-DDP + DTX and iv) CBDCA + DTX. The approach provides individual drug response patterns of epithelial as well as of stromal cells. Individual, selective sensitivities were found for each drug combination tested. The stromal and epithelial chemoreactivity profiles differed in most of the specimens. Moreover, stromal cell chemoresistance dominated selective epithelial chemosensitivities in the majority of cases. The determination of the epithelial ex vivo chemoreactivity identified individual chemosensitivities which were verified by the clinical history of the patient. Therefore, the described protocol to determine the ex vivo chemoresponse of HNSCC specimens to cytostatic drug combinations may help to provide clinicaly useful information concerning the individual chemoresponse of HNSCC with regard to individualization of oncological decision making.

Ex vivo responsiveness of head and neck squamous cell carcinoma to glufosfamide, a novel alkylating agent.

BACKGROUND: Glufosfamide is a novel alkylating agent in which the active metabolite of isophosphoramide mustard is glycosidically linked to beta-D-glucose. Targeting the elevated glucose uptake of tumor cells expressing the SAAT1 glucose transporter, glufosfamide represents an attractive new drug for cancer chemotherapy. The present study investigates the ex vivo responsiveness of Head and Neck Squamous Cell Carcinoma (HNSCC) specimens to glufosfamide. PATIENTS AND METHODS: Twenty-one unselected HNSCC specimens were investigated using a novel ex vivo colony formation assay to determine the epithelial drug response. The individual responsiveness to glufosfamide and to cis-platinum was determined. RESULTS: Five out of 21 evaluable HNSCC specimens were sensitive to glufosfamide. There was a tendency for glufosfamide sensitivity in platinum-resistant specimens and vice versa. CONCLUSION: The effectiveness of glufosfamide observed in the present ex vivo study suggests at least an equipotentiality of glufosfamide in comparison to cis-platinum. The potential clinical usefulness of glufosfamide in HNSCC warrants further evaluation.

The impact of stromal cell contamination on chemosensitivity testing of head and neck carcinoma.

BACKGROUND: Reliable chemosensitivity testing of head and neck squamous cell carcinoma (HNSCC) still faces methodical limitations. Since stromal cell contamination has been found to preclude reliable radiosensitivity testing of HNSCC as well as chemosensitivity testing of lung tumors, the present study investigates the impact of stromal cell contamination on chemosensitivity testing of HNSCC. PATIENTS AND METHODS: Seventeen biopsies from HNSCC were analyzed. The specimens were investigated using an ex vivo colony formation assay which allows for the quantitative and separate determination of the overall, as well as the epithelial, and stromal response to carboplatin, 5-fluorouracil and docetaxel. RESULTS: The overall chemoresponse was dominated by stromal cell multidrug resistance. However, by selective evaluation of the epithelial chemoresponse, individual chemosensitivity patterns could be identified. CONCLUSION: Multidrug-resistant stromal cells preclude the reliable assessment of the chemoresponse of HNSCC specimens. Carefiul correction for stromal cell effects is a prerequisite for the generation of therapeutically useful information.

Prognostic impact of reoxygenation in advanced cancer of the head and neck during the initial course of chemoradiation or radiotherapy alone.

BACKGROUND: Previous studies have shown that radiation of hypoxic tumors can result in reoxygenation phenomenon. The relevance of this phenomenon for prognosis is unclear. This study analyzes whether the presence of hypoxia, or the extent to which reoxygenation occurs during the initial phase of primary chemoradiation or radiotherapy, can predict the clinical outcome in advanced tumors of the head and neck. METHODS: The distribution of oxygen partial pressures was determined using pO(2) histography (Kimoc 6650, Sigma pO(2)-Histograph, Eppendorf, Hamburg, Germany). In cervical lymph node metastases of 37 patients with advanced carcinoma of the head and neck (stage IV, UICC), these values were determined before the start of primary chemoradiation or radiotherapy alone (pO(2)x). Thirty-two of 37 patients were reexamined after 1 week of therapy, and measurements were taken again in the same nodes (pO(2)y). The results obtained from these measurements were correlated with both, the initial response to therapy and follow-up results (43 months). RESULTS.: In all patients, pronounced hypoxia (median pO(2), 3.2 mmHg) was found before therapy. In 19 of 32 patients, chemoradiation/radiotherapy induced reoxygenation (deltaO(2) = pO(2)y - pO(2)x), with median deltapO(2) increasing to 6.5 mmHg after 1 week (p =.049). The group of patients with a complete or partial response showed only a slight increase of median deltapO(2) (1 mmHg) compared with a strong reoxygenation effect in the group of patients with no change (mean value of median deltapO(2) = 10.3 mmHg; p =.0062). The group of patients with deltapO(2) values lower than median showed significantly better survival rates compared with the other group (p =.036). CONCLUSION: These data suggest that reoxygenation under therapy may have prognostic relevance in patients with advanced carcinoma of the head and neck treated by primary chemoradiation or radiation therapy. Remarkably, however, a poor outcome was associated with a higher degree of reoxygenation.

Laryngotracheoscopic findings in long-term follow-up after Griggs tracheostomy.

OBJECTIVE: Analysis of laryngotracheoscopic findings of the upper airway tract following percutaneous tracheostomy using the technique according to Griggs. DESIGN: Retrospective cohort study PATIENTS: Nineteen of 32 long-term surviving patients (mean follow-up duration, 17 months; range, 11 to 23 months) underwent a modified Griggs tracheostomy during their stay in the ICU following cardiothoracic surgery. INTERVENTIONS: Nineteen patients gave their informed consent for laryngotracheoscopy to localize and assess the percutaneous dilatational tracheostomy (PDT) puncture site, to evaluate the laryngotracheal morphology, and to quantify tracheal stenosis if present. In addition, specific symptoms of the upper airway tract were evaluated. RESULTS: At the time of examination, no clinically relevant cases of stenoses were found, although one patient had undergone surgical revision of the PDT for extensive granulation prior to our examination. The endoscopic examination revealed that 12 of 19 patients (63%) had tracheal stenoses > 10%, and 2 patients had tracheal stenoses > 25%. In 7 of 19 patients (32%), the cricoid cartilage was affected by the PDT site. Despite endoscopic guidance during PDT, the location of the puncture site was found to vary greatly. CONCLUSION: In contrast to recent reports on the long-term outcome after Griggs PDT, we found tracheal stenoses > 10% in 63% of our patients. The grade of stenosis depended mainly on the puncture site of the PDT. Based on these results, we would emphasize the importance of adequate endoscopic guidance during PDT. Further studies are required in order to clarify the risk of long-term complications arising after PDT using the technique of Griggs.

Long-term outcome after Griggs tracheostomy.

OBJECTIVE: The purpose of this study was to evaluate laryngotracheal stenoses in the long-term outcome after percutaneous tracheostomy. METHODS: Between 1997 and 2000, 162 patients were tracheostomized during their postoperative stay at the intensive care unit of the Department of Cardiac Surgery, University of Heidelberg. Thirty-eight of 80 long-term surviving patients (mean follow-up: 22 months, range: 7-50 months) gave their informed consent to follow-up laryngotracheoscopy. By using this technique, we localized the tracheostomy site, evaluated the laryngotracheal morphology, and quantified laryngotracheal stenosis planimetrically. RESULTS: Clinically relevant stenoses were found in one patient. Another patient had undergone surgical revision of the percutaneous dilatational tracheostomy (PDT) prior to our examination. The endoscopic examination revealed that 89.5% (34/38) of the patients exhibited tracheal stenosis, less than 25% without clinical symptoms. Despite endoscopic guidance during PDT, the location of the puncture site was found to vary greatly. Cricoidal lesions were identified in 15 patients. In only 12 patients (31.6%), the PDT had been placed at the optimal location between the first and the second tracheal ring. In these patients, we found the lowest rate of tracheal stenosis in tracheotomies without fractured tracheal rings. CONCLUSION: Since clinically relevant tracheal stenosis has been found to depend mainly on the puncture site of the PDT and tracheal fractures during PDT, we want to emphasize the importance of adequate endoscopic guidance during and the careful performance of the PDT. Further follow-up studies are necessary to improve and ensure the quality of PDT techniques.