Effects of nasal insufflation on arterial gas exchange and breathing pattern in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure.

High flow nasal insufflations (NI) can improve gas exchange and alleviate dyspnea in patients with acute respiratory failure. In the present study we investigated the effects of high flow nasal insufflations in COPD patients with chronic hypercapnic respiratory failure (HRF). Seventeen patients with severe COPD and HRF were recruited. We delivered a mixture of 20 L/min room air and 2 L/min O(2) through a nasal cannula either into both nostrils (NI) or into one nostril (Partial NI). Respiratory pattern and PaCO(2) responses under NI were compared with low flow oxygen of 2 L/min. High flow nasal insufflations led to a systematic reduction in respiratory rate from 19.8 ± 4.2 at baseline to 18.0 ± 4.7 during NI (p < 0.008) and 18.1 ± 5.2 breaths/min during Partial NI (P < 0.03). The mean group inspiratory duty cycle (T(I)/T(T)) and mean group PaCO(2) remained constant between all experimental conditions. Individual responses to NI were heterogeneous: six patients demonstrated marked reductions in respiratory rate (>20% fall from baseline), another group (n = 6) demonstrated no change in respiratory rate but marked reductions in arterial carbon dioxide of more than 8 mmHg. In conclusion, high flow (20 L/min) nasal insufflations of warm and humidified air during wakefulness for 45 min reduced respiratory rate without deterioration of hypercapnia. Our data indicate that high flow NI improved efficiency of breathing and may be used as an adjunct to low flow oxygen for preventing hypercapnic respiratory failure in severely ill COPD patients.

The contribution of endobronchial ultrasound-guided forceps biopsy in the diagnostic workup of unexplained mediastinal and hilar lymphadenopathy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) provides material for the cytological diagnostic workup. To improve the evaluation of unexplained intrathoracic lymphadenopathy, the availability of material for histological evaluation would be desirable. For this purpose, the technique of endobronchial ultrasound-guided mediastinal forceps biopsy (EBUS-guided forceps biopsy) is a potentially good candidate. The aim of the present study was, using simple methodology, to establish the additional diagnostic yield provided by supplemental EBUS-guided forceps biopsy in comparison with EBUS-TBNA alone. METHODS: The data of 50 consecutive patients with mediastinal, lobar, and hilar space-consuming lesions were analyzed. In all patients, immediately following EBUS-TBNA with a 22-gauge needle, a 21-gauge forceps was introduced through the opening created in the bronchial wall and an EBUS-guided forceps biopsy performed. The improvement in the diagnostic yield was determined. The diagnostic yield of the EBUS-guided forceps biopsy in relation to the size of the biopsy specimen and that of the EBUS-TBNA in relation to the cell-block technique were determined. RESULTS: Combining the techniques increased the diagnostic sensitivity of the EBUS-TBNA from 50.0 to 82.0%. EBUS-guided forceps biopsies measuring ≥ 3 mm enabled a specific diagnosis to be established more often than did forceps biopsies <3 mm (90.9% vs. 57.1%). A cell block was prepared in 29 patients. In this case, EBUS-TBNA provided a higher diagnostic yield (65.5% vs. 28.6%) compared to cytology alone. CONCLUSION: EBUS-guided forceps biopsy should be employed for the bronchoscopic diagnosis of intrathoracic lymphadenopathy of unknown etiology.

Removal of the tracheal tube after prolonged mechanical ventilation: assessment of risk by oscillatory impedance.

BACKGROUND: Decannulation failure is usually due to tracheal obstruction. Prior to decannulation, inspection by the invasive procedure of bronchoscopy that permits morphological evaluation of a tracheal stenosis is standard practice. A non-invasive method enabling the quantification of the airway obstruction that requires little cooperation is measurement of the airway resistance by the forced oscillation technique. OBJECTIVES: The aim of the present study was to define oscillatory impedance thresholds which predict successful decannulation. METHODS: A total of 131 patients were investigated prospectively. Step 1: Following probatory decannulation, measurement of the oscillatory impedance. Step 2: Blinded to the results of the impedance measurement, bronchoscopy-assisted decannulation attempt. The criteria for renewed cannulation were high-grade laryngeal or tracheal obstruction, dyspnea or stridor, or a drop in SaO(2) <90% under O(2) insufflation. STATISTICS: Determination of the ratio tracheal tube remains/tracheal tube removed (TT+/TT-) for every measured value of the oscillatory resistance at 5 Hz (Ros 5 Hz). Determination of specificity and positive predictive value for determined threshold values with respect to TT-. RESULTS: The data of 126 patients were evaluated. TT+ n = 26, TT- n = 100. Decannulation on the basis of bronchoscopy criteria: Specificity and positive predictive value found out for Ros 5 Hz <0.35 kPa/l/s (n = 44) were 1.00 and 1.00, respectively, and for Ros 5 Hz <0.47 kPa/l/s (n = 71) 0.88 and 0.96, respectively. CONCLUSIONS: Measurement of the oscillatory airway resistance represents a practicable method prior to decannulation. Below a value of Ros 5 Hz <0.35 kPa/l/s, bronchoscopy would appear not to be necessary.

Quality of life, compliance, sleep and nasopharyngeal side effects during CPAP therapy with and without controlled heated humidification.

PURPOSE: To determine the effect of a controlled heated breathing tube humidifier (cHH) on the quality of life (QOL), compliance and nasopharyngeal side effects during continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea syndrome (OSAS) in comparison with conventional CPAP. METHODS: In this prospective randomised cross-over study, 44 patients with OSAS were investigated. During the first two consecutive treatment nights monitored by polysomnography, patients were randomly assigned to receive CPAP with or without cHH. Patients were then randomised to receive one of the treatment modalities at home for 4 weeks. Compliance was recorded and questionnaires assessing side effects and QOL were administered. RESULTS: Sleep parameters measured during the nights in the sleep laboratory did not change. The same result applied to QOL and compliance measured after 4 weeks. During the first two nights we found significant differences between CPAP with and without cHH for dryness of mouth (2.0 ± 1.4 vs. 1.4 ± 1.6) in favour of cHH (p < 0.05). Evaluation of coldness of the face showed improvement whereas waking up due to wetness on the face (0.3 ± 0.6 vs. 0.6 ± 0.8; p < 0.05) was slightly increased. Data after 4 weeks confirmed these findings with further subjective improvement in the reduction of side effects. CONCLUSIONS: By the using of the technology of cHH QOL and compliance did not improve. The side effects of CPAP therapy without humidification with respect to nasopharyngeal dryness, however, was reduced immediately as well as during the first weeks of treatment.

Prospective controlled animal study on biopsy sampling with new flexible cryoprobes versus forceps: evaluation of biopsy size, histological quality and bleeding risk.

BACKGROUND: Cryoextraction is a procedure used for the recanalization of obstructed airways caused by visible exophytic endobronchial tumor. Biopsy samples obtained by this technique have been shown to be useful for histological assessment. OBJECTIVES: The aim of the present animal study was to systematically evaluate biopsy size, histological quality and bleeding risk after cryobiopsy with new, flexible cryoprobes in comparison with forceps biopsy, serving as the gold standard. METHODS: Biopsies were obtained from anesthetized pigs with the flexible bronchoscopy technique, and evaluated histologically with respect to their size and quality. Bleeding frequency, bleeding duration and histological changes in the biopsy bed were also recorded. RESULTS: Cryobiopsies were significantly larger than forceps biopsies. The size of cryobiopsies was dependent on the freezing time. The histological quality of the cryobiopsy specimenswas not impaired by the freezing process, whereas forceps biopsies showed typical crush artifacts. Despite the larger defects left in the tracheobronchial system after cryobiopsy, bleeding frequency and duration were not higher compared to forceps biopsy. CONCLUSIONS: Since cryobiopsy sampling is not associated with a higher bleeding risk compared with forceps biopsy, this new biopsy technique offers--in addition to a good specimen quality--a safe and valuable tool with the potential of improving the outcome of diagnostic endoscopy.

Treatment of malignant pleural effusion with the trifunctional antibody catumaxomab (Removab) (anti-EpCAM x Anti-CD3): results of a phase 1/2 study.

Catumaxomab is a trifunctional monoclonal antibody consisting of a mouse immunoglobulin G2a part and a rat immunoglobulin G2b part with 2 different antigen binding sites binding the epithelial cell adhesion molecule antigen on tumor cells and CD3 on T lymphocytes. The intact Fc region provides a third functional binding site, binding and activating selectively Fcgamma receptor I, IIa, and III-positive accessory cells. These binding properties lead to specific tumor cell killing. As catumaxomab demonstrated efficacy in patients with malignant ascites, we performed this phase 1/2 trial in patients with malignant pleural effusion (MPE). We investigated a series of 3 escalating doses of 5 to 200 microg catumaxomab administered intrapleurally to patients with MPE containing epithelial cell adhesion molecule -positive cells. Primary objectives were determination of dose-limiting toxicity, safety, and tolerability. Secondary objectives were efficacy and pharmacodynamics. Twenty-four patients were treated with catumaxomab. Most frequent adverse events were pyrexia, elevated liver enzymes, nausea, and decreased lymphocytes. Dose-limiting toxicities were observed in 2 patients: One had pleural empyema and fatal sepsis and 1 had grade 3 erythema and hepatobiliary disorder. Five patients with breast cancer out of 7 evaluable patients had a response to treatment. Intrapleural administration of catumaxomab is feasible although the substantial number of drop-outs and deaths in short proximity to study treatment raise questions whether MPE is the right indication for catumaxomab or whether the patient population should be defined different. Safety profile was as expected reflecting catumaxomab's mode of action. Preliminary efficacy showed a suggestion of improvement in some patients.

Mouth breathing in obstructive sleep apnea prior to and during nasal continuous positive airway pressure.

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) often complain of dryness of mouth and throat prior to and during nasal continuous positive airway pressure (nCPAP). It is believed that this is due to mouth breathing (MB). However, the association between mouth breathing and apneas/hypopneas and the effect of CPAP on MB has not been studied. OBJECTIVES: The purpose of the present study was, therefore, to assess the frequency and duration of episodes of MB prior to and during treatment with nCPAP. METHODS: MB was recorded prior to and during nCPAP with a closely fitting mouth mask connected to a pneumotachograph and nasal flow was measured via nasal prongs. MB episodes were expressed as the number of events divided by total sleep time x 60, to give the MB event index per hour of sleep. MB time divided by total sleep time x 60 was calculated in minutes to get the MB time index per hour of sleep. PATIENTS: Eleven male patients with OSAS (mean age 57.9 +/- 8.3 years, body mass index 30.2 +/- 3.8) were recruited to the study. RESULTS: Prior to nCPAP, the apnea/hypopnea index was 55.8 +/- 26 and decreased during nCPAP to 8.0 +/- 3.4. The lowest SaO2 measured was 82.9 +/- 4.7%, and increased to 87.5 +/- 2.7% under nCPAP. The mean nCPAP was 7.8 +/- 1.6 cm H2O. MB event index per hour of sleep decreased from 35.2 +/- 19.7 prior to treatment to 5.0 +/- 5.2 under nCPAP (p < 0.01). In 52.2 +/- 27.4% of obstructive respiratory events, MB started at the end of an apnea/hypopnea episode, decreasing to 8.5 +/- 12.5% with nCPAP treatment. MB time index per hour of sleep was reduced from 13.5 +/- 10.2 min prior to treatment to 4.6 +/- 5.5 min under nCPAP (p < 0.05). CONCLUSIONS: In OSAS patients, MB episodes often appear at the termination of an apnea/hypopnea episode. In many cases, MB episodes can be markedly reduced by nCPAP treatment. When patients on nCPAP complain of dry mouth, appropriate measurements should be performed to verify MB.

Pressure-relief continuous positive airway pressure vs constant continuous positive airway pressure: a comparison of efficacy and compliance.

OBJECTIVES: To compare polysomnographic data and compliance in sleep apnea patients receiving continuous positive airway pressure (CPAP) and pressure-relief CPAP (PRCPAP) [C-flex; Respironics; Murrysville, PA] as first treatment in the sleep laboratory and subsequently at home. DESIGN: A prospective, randomized, crossover design was used in the sleep laboratory, and a prospective randomized design was used at home. PATIENTS: Data were collected from 52 sleep apnea patients for whom CPAP was used for the first time. INTERVENTIONS: Treatment with constant CPAP and PRCPAP. MEASUREMENTS AND RESULTS: Patients with a first-time diagnosis of obstructive sleep apnea syndrome (OSAS) underwent conventional CPAP titration. Thereafter, polysomnography was performed at the titrated pressure using both the fixed CPAP pressure mode and the PRCPAP mode in a randomized crossover approach. The patients were then discharged home for 7 weeks of treatment with the last-applied treatment mode, and compliance data were established at the end of that time. The average apnea-hypopnea index was 53.3/h in the "diagnostic night," 5.8/h with CPAP, and 7.0/h with PRCPAP. The native arousal index was 35.2/h, 12.6/h with CPAP, and 12.9/h with PRCPAP (not significant [NS]). The central apnea index was 0.7/h with CPAP and 1.2/h with PRCPAP (p < 0.05). Compliance after 7 weeks was, on average, 9.4 min longer with PRCPAP than with CPAP (NS). Evaluation of a 13-item questionnaire showed scores of 16.4 for PRCPAP and 18.1 for constant CPAP (NS) [the fewer the complaints, the lower the score]. With regard to oral dryness, the score with PRCPAP (1.4) was significantly lower than with constant CPAP (1.9) [p < 0.05]. This difference was no longer detectable after 7 weeks. CONCLUSION: In terms of the effectiveness in treating obstructive sleep apnea, PRCPAP and constant CPAP are comparable. During the first night of treatment, patients receiving PRCPAP had less dryness of mouth; over a period of 7 weeks, this difference disappeared. Nightly use of the device was comparable in both groups. PRCPAP is therefore a new ventilation mode that enables effective treatment of OSAS patients. Further studies should be done to investigate the effects of expiratory pressure lowering in low-compliance patients and patients requiring CPAP > 9 cm H(2)O or experiencing dry mouth with CPAP.

Tongue-muscle training by intraoral electrical neurostimulation in patients with obstructive sleep apnea.

STUDY OBJECTIVES: To investigate the efficacy of tongue-muscle training by electrical neurostimulation of the upper-airway muscles as an alternative therapy option for obstructive sleep apnea syndrome. DESIGN: A randomized, placebo-controlled, double-blind study. SETTING: Department of pneumology and sleep laboratory, University of Witten/Herdecke, Germany. PATIENTS: 67 patients with an apnea-hypopnea index of 10 to 40 per hour were randomly assigned to 2 groups: a treatment group of 33 patients (mean age, 50.8 +/- 12.1 years; mean body mass index, 29.1 +/- 4.4 kg/m2) and a placebo group of 34 patients (mean age, 53.3 +/- 11.3 years; mean body mass index, 28.9 +/- 4.9 kg/m2). Fifty-seven patients completed the study. INTERVENTIONS: Tongue-muscle training during the daytime for 20 minutes twice a day for 8 weeks. MEASUREMENTS AND RESULTS: Treatment efficacy was examined by polysomnography. Snoring, but not apnea-hypopnea index, improved with stimulation (snoring baseline, 63.9 +/- 23.1 epochs per hour; stimulation training, 47.5 +/- 31.2; P < .05) but not with placebo training (snoring baseline, 62.4 +/- 26.1 epochs per hour; placebo, 62.1 +/- 23.8; NS.). CONCLUSIONS: Although tongue-muscle training cannot generally be recommended for the treatment of sleep apnea, the method has proven to be effective in the treatment of snoring.

Auto-adjusting CPAP based on impedance versus bilevel pressure in difficult-to-treat sleep apnea syndrome: a prospective randomized crossover study.

BACKGROUND: Although continuous positive airway pressure therapy (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS), there is a portion of patients in which CPAP is not usable. Bilevel treatment serves as an alternative for these patients. For uncomplicated OSAS, auto-adjusting CPAP based on the forced oscillation technique (APAPFOT) has proved to be equally as effective as constant CPAP, and is preferred by the patients. The aim of this study was to investigate the question whether, in the event of primary CPAP intolerance, high pressures (>or =12 cm H2O) or SAS with > or =10% central respiratory disorders, APAPFOT is as effective as bilevel therapy in reducing respiratory disturbances. MATERIAL/METHODS: 27 patients (23 m, 4 f, age 57.2+/-13.1 years, BMI 33.5+/-7.8 kg/m2) were treated with bilevel and APAPFOT for 6 weeks each in a prospective randomized cross-over study. The efficacy of the treatment modes was examined polysomnographically. RESULTS: Both modalities significantly improved the respiratory disturbances (AHI: baseline 49+/-27.3/h, bilevel 9.8+/-12.5, p<0.01, APAPFOT 13.8+/-13.2, p<0.01) and sleep quality (arousals: baseline 43+/-28.3/h, bilevel 17.7+/-8.8, p<0.01, APAPFOT 20.5+/-10.7, p<0.01), with no significant differences between the modalities. Under APAPFOT, mean treatment pressure was substantially reduced (bilevel 8.3+/-2.5, APAPFOT 5.1+/-1.7, p<0.01). The majority of patients gave preference to APAPFOT for long-term treatment (21 vs. 6 patients, p<0.05). CONCLUSIONS: In patients with difficult-to-treat OSAS, APAPFOT has proved to be just as effective as bilevel therapy, but has the advantage of meeting with greater acceptance.