TNI 20: Breathe Easier without a Mask

TNI 20: Breathe Easier without a Mask

TNI 20 is for many patients a much more comfortable alternative to positive pressure respiration (CPAP) and other methods to treat sleep-related breathing disorders because it is an open system and functions without a mask or closed nasal prongs. The patented, worldwide unique TNI method brings significant improvement in comfort for many affected patients, as well as a reduction in the side effects of the therapy. Using an extremely thin tube, this open system revolutionizes the therapy of sleep-related breathing disorders. Breathe Easier without a Mask

Benefits of TNI 20: An open system without a mask increases wearing comfort, eliminates pressure points on the face and is very easy to put on and take off. There are no leakage problems, and therefore no resulting eye inflammations or loud noises that vary with breathing. A very thin tube and a nasal applicator allow the patient to maintain his normal sleeping positions, for example it is possible to sleep on one s stomach. The system s warm, humid air prevents the nose and mouth from drying out. The system is easy to use and clean. The blower unit is separate and can be placed outside the bedroom.

TNI blows a stream of warm, humid room air at a rate of about 20 liters per minute over a nasal applicator into the patient s nose. The nose remains open, is not closed in the process, and therefore simple breathing out is ensured. With a quiet blower, the device generates compressed air which is humidified and warmed in a humidifier filled with normal tap water. An ingenious automated control ensures the correct humidity and temperature, no matter whether the user happens to be in a cool and dry or warm and damp environment. Depending on the individual settings of the device and the prevailing ambient conditions, a relative humidity is maintained at the nose between 60% and 80%, and a temperature of about 5 to 15 C above the room temperature.

TNI is wholly non-hazardous and simple to use. The system includes a blower unit, a humidifier unit and an applicator. The following table provides you with the most important technical data: Medical product class IIa Operating voltage: 100-240 Volt / 50-60 Hz Noise radiation: <32dB(A) Weight: blower unit approx. 8.5 kg humidifier unit approx. 2 kg Dimensions: blower unit 26/22/23.5 cm humidifier unit 26/22/10 cm Applicator: silicone, length approx. 1.8 m, diameter approx. 5 mm and 7 mm TNI 20 the System

The effectiveness of the TNI for sleep apnea and diverse pulmonary diseases has already been confirmed by numerous clinical trials and studies in Germany and the USA.* Experience gained to date has shown that the TNI has been very well accepted by most patients. Both the warm and moist airflow as well as nasal applicator with the thin tube contribute to the comfort of the therapy. * Brown C et al 2007, Proc. Am. Thor. Soc. 2007 McGinley B et al 2007, Am. J. Resp. Crit. Care Med. 176(2) McGinley B et al 2007, Somnologie 11 Nilius G et al 2007, Somnologie 11

Where can I test or buy TNI 20? Please speak with your physician about the possibility of using or testing the TNI in connection with your individual symptom complex. You can find more information at www.tni-medical.com or you are welcome to contact our team: e-mail: info@tni-medical.de phone: +49 761 21 430-0. Approved for the European Market! Please note: this product may not be available in your country due to approval reasons. Study and Test Results

Breathe easier without a mask: TNI is worldwide the only respiratory support system without a mask. A revolution for those affected. TNI medical AG Engesserstraße 4a 79108 Freiburg Germany Phone +49 761 21 430-0 Fax +49 761 21 430-100 info@tni-medical.de www.tni-medical.com

TNI 20: A revolution for those needing breathing therapy.

TNI : The new breathing therapy without mask TNI (Treatment with Nasal Insufflation) conducts a warm, moistened flow of room air of maximum 20 liters air per minute to the patient over a special, particularly quiet applicator (nasal applicator) in the nose. The nose remains open, is hence not covered by a mask as with CPAP therapy. Simple exhaling is ensured. The open system without mask or closed nasal prongs is thus an extremely comfortable alternative to positive pressure respiration and other methods for treating sleep-related breathing disorders. The worldwide only and patented method (TNI ) represents a significantly improved therapy for many affected persons. Side effects of the previous therapy by positive pressure respiration, caused for instance by the pressure of the mask on the face, leakages or lack of nasal humidification, are excluded. Only accounts of a pronounced therapy loyalty have been reported to date. This open system represents a revolutionary therapy for sleep-related breathing disorders, using a tube only a few Millimeter thick. TNI 20: A technical challenge The TNI 20 device generates compressed air with a blower unit. The air is warmed up in a humidifier filled with normal tap water. An ingenious automated control system ensures the proper humidity and temperature, whether the user's environment is cool or warm, dry or moist. Depending on the individual setting on the device and existing ambient conditions, it is possible to achieve a relative humidity (60-80%) and an increased temperature (5-15 C above room temperature). TNI 20 is extremely easy to use. It is not necessary to set the pressure. The system consists of a blower unit, a humidifier unit and the nasal applicator. The following table provides a summary of the most important technical data: Medical technology device class 2a Operating voltage 100-240 Volt / 50-60 Hz Weight Blower unit: 8.5 kg Humidifier unit: 2 kg Size Blower unit: Humidifier unit: Applicator: Material: 26/22/23.5 cm 26/22/10 cm length: 1.80 m diameter: 5 and 7 mm Cawiton / Silicon Breathe more freely with TNI

TNI 20: Advantages Open system without mask, consequently high patient comfort, no pressure points on the face, very simple to take on and off. No leakages or their related consequences such as eye infections or loud noises varying with the breathing cycle. Very thin applicator tube (nasal applicator): usual body position can be retained during sleep, also on stomach. Integrated air humidification and warming: nose and mouth do not dry out. Easy to use, simple operation and cleaning of the device. Separate blower unit which can be placed outside the bedroom. Can be easily tested individually, since non-invasive, reversible and poses no hygienic risk to health. No known side effects. TNI 20: Range of applications The TNI 20 range of applications as a whole is seen as the somewhat more filigree breathing therapy. Studies conducted at Johns Hopkins University Hospital in Baltimore and a recent study in 4 German sleep centers show that in fact an effectiveness over the entire spectrum of serverity can be seen in approximately one third of all patients. For patients with UARS, primarily REM related OSA and patients suffering from hypopneas, the method demonstrates good effectiveness 2. In addition, TNI has already been used successfully as substitute therapy for patients with more severe symptom complexes who do not tolerate CPAP. For children, there is a very high effectiveness across the entire spectrum of breathing disorders 3. It is especially difficult to motivate children to wear a breathing mask 4. For this reason TNI is in any case the therapy of choice for children. Currently numerous studies are being conducted on different related clinical and scientific questions.

TNI : How does it work? The operative principle of the TNI 20 can essentially be explained in the context of three interacting mechanisms: 1) Measurable increase of the pressure in the upper respiratory tract: also with an open system a pressure is built up, a so-called pneumatic splint, by increasing the resistance to the outside 1. Depending on the individual anatomy, this pressure amounts to between 2 and 4 mbar at a flow of 20 liters per minute. 3) There are indications that neurological feedback mechanisms play a role, since for on / off experiments with the TNI the effect on the respiratory drive is often only delayed by a few breaths (Figure 2). Approved for the European Market! Please note: this product may not be available in your country due to approval reasons. 2) Measurable increase of the Positive End Expiratory Pressure (PEEP): TNI increases the PEEP by about 1 to 2 mbar, and thus effectively relieves respiration. For a given collapsibility of the upper respiratory tract, partial closures and / or closures in the pharynx are reduced due to less breathing exertion and thus fewer pressure fluctuations (Figure 1). 1 McGinley, B. et al., A Nasal Cannula can be used to treat obstructive sleep apnea, in American Journal of Respiratory and Critical Care Medicine 2007; 176; 194-200 2 Nilius, G. et al., Multicenterstudie zur Wirksamkeit der transnasalen Insufflation (TNI ) bei leichter bis mittelgradiger pharyngealer Obstruktion und Schlafapnoe, in Somnologie 2007; 11, Supplement 1; 26 [conference abstract] 3 McGinley, B. et al., A Nasal Cannula (TNI ) Treats Pediatric Obstructive Sleep Apnea, in Somnologie 2007; 11, Supplement 1; 26 [conference abstract] 4 Marcus, C. L. et al., Adherence to and Effectiveness of Positive Airway Pressure Therapy in Children With Obstructive Sleep Apnea, in Pediatrics 2006; 117; 442-451 DOI: 10.1 542 / peds. 2005-1634 Application and operative principle

Figure 1: PEEP: Positive End Expiratory Pressure Figure 2: Flow Flow 20l/m 11:30 pm 20l/m 11:30 pm Esophagus pressure Esophagus pressure 20l/m 11:30 pm PEEP without TNI PEEP with TNI 20l/m 11:30 pm Slight pressure fluctuations in the pharynx with TNI prevent falling below the critical pressure for collapsibility. TNI ON Substantial stabilization only after 6 to 7 breaths Improvement of breathing flow and snoring starts with time delay.

TNI medical AG Engesserstraße 4a 79108 Freiburg Germany Phone +49 761 21 430-0 Fax +49 761 21 430-100 info@tni-medical.de www.tni-medical.com

TNI 20s / TNI 20s oxy: A revolution for those needing breathing therapy with optional oxygen.

TNI 20s / TNI 20s oxy Treatment with Nasal Insufflation A worldwide unique and novel method of ventilatory support, TNI, was first introduced during January 2006 in Germany for the treatment of sleep disordered breathing. For patients, the nasal insufflation of a high flow of warmed and humidified air, TNI, is a much more comfortable and uncomplicated alternative to numerous other approaches in non-invasive ventilation (NIV). Up to now, NIV therapy could only be applied by nasal masks or full face masks with the associated complications, because patients could not tolerate high airflow delivered by a thin nasal cannula without humidification and warming, and because of concomitant negative aspects. The new therapy TNI shows a high rate of acceptance by children, too. In addition, TNI 20s oxy the version of the product supporting oxygen blends opens the way for new strategies in the application of oxygen ventilation. This unique system is optimized for flow rates up to 20 l/min. It fulfils both the minimum requirement defined by ASTM International (originally the American Society for Testing and Materials) for high-flow air humidifiers used in non-invasive ventilatory treatment and the requirements of the international norm for humidifiers for medical use (ISO 8185) of 10 mg H 2 O/l for the humidity (equivalent to around 60% relative humidity at 22 C (72 F) ambient temperature). The device can be regulated to warm the air flow by 5 10 C (41 50 F), depending on the ambient temperature. TNI 20s and TNI 20s oxy operate within the clinical infrastructure using provided pressure regulators. Note: TNI 20s and TNI 20s oxy are not suited for ventilation in basic life support. High comfort, simple handling in daily clinical routine No need to handle complicated settings for the regulation of pressure or volume, so this therapy can be provided to patients within minutes also by staff without specific training The very thin tube involves minimal discomfort, and with no fixation on the head it is quickly attached and detached, so patients can be more easily motivated to use the system Quiet, sound-optimized nasal cannula Open system when alert, patients can speak, eat and drink with only minimal inconvenience The device automatically regulates warmth and humidification relative to room temperature Tubes warmed all the way to the nostrils reliably prevent condensation The concomitant negative aspects of NIV are not encountered here no dryness or damage of the mucous membranes on prolonged ventilation with oxygen Sanitizing is uncomplicated the water reservoir made of stainless steel can be cleaned and sterilized according to the standard procedures for all other polished stainless steel containers TNI 20s uses medicated air and TNI 20s oxy additionally offers the option of mixing in clinical oxygen. Note: this product may not be available in your country due to approval reasons. Breathe easier with TNI

Safe and advantageous in both use and maintenance To date, no significant side effects have been reported beyond some complaints of a tickling sensation in the nose which ceases as a rule within a few minutes. The same applies upon regular use for the duration of several weeks. To use the device briefly for testing the effectiveness is in most instances completely free of risk. Patients never exhale and rebreath into this device on replacement of the nasal cannula the TNI is ready for use again with an easy and quick cleaning procedure. The TNI humidifying function operates at a temperature up to 60 C (140 F). This temperature range is low enough that serious burns will not result from incorrect handling, e.g. if patients or staff were to reach inside. All airconducting parts of the device are readily accessible for daily cleaning. The devices, components and the only disposable material, the applicator, are clearly advantageous in comparison with all other ventilation equipment. As described above, simplification of the everyday usage and of the cleaning combine to make TNI a very advantageous method of ventilatory support in routine clinic use. Mechanisms of ventilatory support Measurements taken at the Johns Hopkins Hospital in Baltimore 1 (USA) and further clinical studies 2 have shown that breathing is effectively supported by high-flow ventilation, for example with TNI (Fig. 1). 400 Flow (ml/s) -400 P Supraglottic (cmh 2 0) TNI off 2 0-15 Expiration Inspiration Fig.1: Breathing response on TNI TNI 20 l/min P EEP A positive end-expiratory pressure (PEEP) is built, which leads to an increase of the maximal inspiratory flow and to an increase of the tidal volume. This supportive effect increases ventilation and lowers the work of breathing. As a result, a reduction of respiratory frequency is also observed. This comparatively comfortable method of ventilatory support has great potential in clinical therapy in addition to its application in sleep medicine. 1 McGinley B et al (2007): A Nasal Cannula Can Be Used to Treat Obstructive Sleep Apnea, Am. J. Respir. Crit. Care Med. 176(2):194-200. 2 Ciccolella DE et al (2001): Administration of high-flow, vapour-phased, humidified nasal cannula air (HF_HNC) decreases work of breathing (WOB) in healthy subjects during exercise, Am. J. Respir. Crit. Care Med. 163(5) Part 2: A622 A revolution for those needing breathing therapy

Potential therapeutic indications Ventilatory support in pediatric medicine Previous studies have shown high-flow therapy, for example TNI Therapy, equivalent to noninvasive ventilation in the treatment of small children 3. The results of ongoing research at the Johns Hopkins University Hospital in Baltimore allow the conclusion that this also applies when a proportionally higher flow is used for the treatment of children at a later age. In single incidents, high-flow therapy has provided successful ventilatory support when used post-extubation 4 for children who suffered respiratory insufficiency, possibly even to prevent an intubation 5. Ventilatory support in combination with oxygen therapy Research studies have shown that the oxygen content in the inspired air (FIO 2 ) and oxygen saturation in the blood (SpO 2 ), both coupled with a reduction of the respiratory frequency, were greater when high-flow oxygen therapy was given than when NIV was applied with a mask 6,7. Additionally, a decreased breathing rate was observed. In summary, the available research shows many potential indications for TNI in the clinic and for patients at home: Ventilatory support at COPD 8 (chronic obstructive pulmonary disease), specifically during sleep Post-operative ventilatory support Prophylactic therapy after cardiac surgery Ventilatory support after extubation Ventilatory support after anesthesia Asthma 9 Cystic fibrosis Neuromuscular and thoracic diseases such as post-tuberculosis syndrome and post-polio syndrome Diseases with severe chronic hypoxemia (e.g. pulmonary hypertension) 7 Rehabilitation after lung diseases 10 Weaning from ventilation Overlap syndrome Application in the home TNI is also available in a competitive version for home care. It uses a very quiet and reliable air source, which was originally developed for therapy in the field of sleep medicine. This also allows nightly use without difficulty. An advanced device version, TNI 20 oxy, allows mixing oxygen into the applied air during home use by using a standard medical oxygen source, for example an oxygen concentrator. A re-integration in familiar surroundings at home is possible earlier and with less difficulty. This is no longer a choice between losing ventilatory support and arranging for expensive and complicated care. 3 Sreenan C et al (2001): High-flow nasal cannulae in the management of apnea of prematurity: A comparison with conventional nasal continuous positive airway pressure, Pediatrics 107(5):1081-3. 4 Frick J et al (2004): Vapotherm: A Simple Device becomes a Simple Solution in the PICU, Respir. Care 49(11):1392 [conference abstract]. 5 Byerly L et al (2006): Use of high flow nasal cannula on a pediatric burn patient with inhalation injury and post-extubation stridor, Burns 32: 121-125. 6 Walsh J (2002): Winning by a nose. Advance for Respiratory Practioners 22. 7 Tiep B. & Barnett M. (2002): High flow nasal vs. high flow mask oxygen delivery: tracheal gas concentrations through a head extension airway model, Respir. Care 47(9). 8 Chatila et al (2004): The Effects of High-Flow vs Low-Flow Oxygen on Exercise in Advanced Obstructive Airways Disease, Chest 126:1108-1115 9 Chen WY & Chai H (1982): Airway Cooling and Noctural Asthma, Chest 81:675-680 10 Donna Hawk (2005): Case report: Alpha-1 Antitrypsin treatment with Vapotherm during exercise, Respir. Care November 2005. Indication and mechanism

TNI medical AG Engesserstraße 4a 79108 Freiburg Germany Phone +49 761 21 430-0 Fax +49 761 21 430-100 info@tni-medical.de www.tni-medical.com