Device for providing continued breath guidance, method of operating an inhalation device, inhalation device and inhalation device system for providing inhalation process / breath guiding

Abstract

The present disclosure and invention relates to a device for providing continued breath guidance, a method of operating an inhalation device, an inhalation device and an inhalation device system for providing inhalation process / breath guiding. The devices and procedures provide information about an ongoing inhalation process to the user / patient and further provide preferably continuous inhalation process / breath guiding information so as to enable the patient to improve an ongoing inhalation process if it is found to be non-optimal.

Description

[0001] DEVICE FOR PROVIDING CONTINUED BREATH GUIDANCE , METHOD OF OPERATING AN INHALATION DEVICE , INHALATION DEVICE AND INHALATION DEVICE SYSTEM FOR PROVIDING INHALATION PROCESS / BREATH GUIDING

[0002] TECHNICAL FIELD

[0003] The present disclosure and invention relates to a device for providing continued breath guidance , a method of operating an inhalation device , and inhalation device and an inhalation device system all preferably for providing preferably continuous inhalation process / breath guiding for a user, patient , caregiver, and / or physician .

[0004] Further comprised in the present disclosure and invention is an inhalation method that is optionally related to the above-mentioned method of operating an inhalation device , the inhalation device , and an inhalation device system . Also comprised is an optionally related computer program. Also all preferably for providing inhalation process / breath guiding for a user, patient , caregiver, and / or physician .

[0005] Further comprised in the present disclosure and invention is a device for providing continued and real-time breath guidance when using an aerosol nebulizer system or inhalation device system during an inhalation session .

[0006] BACKGROUND

[0007] With existing medical inhalation devices and nebulisers , a patient breathes as he or she thinks is good and normally gets no feedback and information about the ongoing inhalation process . So , currently there may be a lack of monitoring of an ongoing inhalation process and at the same time an opportunity to provide inhalation or breath guidance is missed . If an inhalation process would be monitored while it is conducted and information relating to a pertinent inhalation process parameter output , then a user / patient could be put in a position to improve the inhalation process while it is conducted .

[0008] EP 2 797 652 Al and US 10 471 122 disclose inhalation devices configured to output signals that to some extent inform a user / patient about aspects of an ongoing inhalation process .

[0009] SUMMARY

[0010] Ob j ective

[0011] It is an obj ective of the present disclosure and invention to provide devices and procedures that allow a user / patient and a physician or caregiver to be given information about an ongoing inhalation process that can in turn provide a basis for the user / patient to improve the inhalation process while the process is conducted . Hence , it is desired to provide devices and procedures that provide inhalation process or breath guiding with respect to an ongoing inhalation process using a medical inhalation device .

[0012] Solution

[0013] The above obj ective is achieved and the above-mentioned advantages realized by the devices and procedures outlined in the present disclosure and invention, in particular the method of operating an inhalation device , the inhalation device and inhalation device system described herein below . Preferably, the present invention is further defined by the appended independent claims , whereas the dependent claims define optional features and distinct embodiments .

[0014] Advantages

[0015] Based on the present disclosure and invention, a user / patient of an inhalation device and a physician or caregiver are put in a position to assess whether an ongoing inhalation process is performed well . If deficits or room for improvement is identified during the ongoing inhalation process , then this will be accordingly communicated to the user / patient or physician or caregiver and gives the opportunity for "live" improvements during the ongoing inhalation process .

[0016] The user / patient then acts more conf idently during the ongoing inhalation process and potentially also feels somewhat safer in performing it . In addition, the present therapy quality can be significantly improved since the user / patient or physician / caregiver is informed about deficits and additionally provided with indications how to improve an ongoing inhalation process . In clinical trials , it can thus be contributed to an improved inhalation process that is closer to prescribed parameters and that thus the clinical trials are meaningful . Generally, in particular continuous breath guidance can reduce variations during an inhalation processes and sessions and thus improve the overall inhalation and therapeutic quality .

[0017] BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Fig . 1 shows a control device according to an example and embodiment of the present disclosure and invention in combination and communication interaction with an aerosol nebulizer system.

[0019] DETAILED DESCRIPTION

[0020] The present disclosure and invention comprise a method of operating an inhalation device that includes : a sensing unit configured to monitor an inhalation process , to measure inhalation process parameters and to collect data of and during the inhalation process , and a control unit configured to receive and process the data collected by the sensing unit and to generate a control signal for a signalling device , wherein the method comprises : monitoring an inhalation process comprising measuring inhalation process parameters and collecting data of and during the inhalation process , generating and sending a control signal based on the collected data to a signalling unit configured to output a signal , preferably an optical , acoustic and / or a tactile signal , wherein in response to said control signal , the signalling unit outputs : a first signal if and whenever a first pre-set threshold value of an inhalation process parameter is underrun or exceeded during the inhalation process and a second signal if and whenever a second pre-set threshold value of an inhalation process parameter, that is different from the first pre-set threshold value , is underrun or exceeded during the inhalation process and / or a third signal that is indicative of one or more inhalation process parameters and continuously output during part or all of the inhalation process .

[0021] The expression "inhalation device" as used in the present disclosure and invention relates to a medical device , i . e . , a medical inhalation device that is used for the prevention and treatment of respiratory malfunctions and diseases in humans or animals , but also for improving wellbeing and as prophylaxis . Said device , in line with the s killed person' s common understanding , at least comprises a mouthpiece-part through which a user / patient is able to or inhales a suitably prepared medicament according to a prescription of a physician or any other suitable agent including salt water and nonprescription medicaments and any type of aerosols . "Nebulizer" devices are also embraced . The expression "inhalation device" in fact embraces all devices suitable and configured for such functionality and purpose , preferably in the medical field or for wellbeing and prophylaxis .

[0022] An "inhalation process" is a process carried out using the above explained "inhalation device" and is conventionally a process in which a user / patient inhales a medicament or any suitable agent by means and through the inhalation device for a certain amount of time and during several breath cycles . The terminology "inhalation process" is a generic term that embraces several complete breaths or breath cycles , respectively, i . e . , inhalations and exhalations per time period . The plurality of inhalations and exhalations of a user or a patient is also referred to as "inhalation session" herein . In the context of the present disclosure and invention, the inhalation part thereof takes centre stage since it is the part of the breath / breath cycle with which a medicament or agent is inhaled and administered and thus preferably most important to be monitored and optimized . Monitoring and optimization of exhalation is by no means included here and fully embraced by the present disclosure and invention where needed . Said inhalation process usually has a beginning at which the inhalation starts and has an end at which inhalation stops . Therebetween a certain amount of time lapses in which the user / patient performs a certain number of breath cycles , i . e . , inhalation and exhalation cycles depending on the specifics of the respective therapy or treatment , preferably at least 3 to 5 breaths / breath cycles . The totality of the time passed and / or the breath cycles defines the inhalation process as such and in its totality and as indicated above include inhalation and exhalation as part of a natural breath / breath cycle . The present disclosure and invention preferably comprises that the inhalation process to be monitored is only part of the totality of the time elapsed and the breath cycles taken . The inhalation process is preferably monitored throughout by the present procedures and devices . Preferably, although in principle possible , the concepts of the present disclosure and invention are not applied to "MDI"-processes ( "metered-dosed inhalation" ) , which do not represent an inhalation process or inhalation session, but normally only a single inhalation and agent burst .

[0023] The "sensing unit" is an entity that is configured to monitor an inhalation process and collect and optionally store data with respect thereto . Said "sensing unit" embraces all suitable means for that and, for example , sensors that are suitably configured to measure pertinent inhalation parameters . The sensing unit is optionally provided and implemented within the inhalation device itself .

[0024] The "control unit" is an entity to be understood broadly and is an " IPO" ( input-process-output ) means that it is configured to receive data , for example , from the sens ing unit , process said data, optionally store the processed data and output said data in order to instruct and control other entities either of the inhalation device itself or externally connected ones . A practical example for such control unit is a microprocessor or microcomputer with respectively configured software stored and executed thereon . The control unit is optionally provided and implemented within the inhalation device itself . Alternatively, the control unit may also be part of an external device similar to the respective option for the signalling unit . The explanations given with respect thereto below then also apply to the control unit .

[0025] Equally broadly is the definition of the "signalling unit" , which is an entity that is configured to output a signal / inf ormation that is preferably recognizable by human senses , for example , audible , visible and tactile signals . As will be detailed below, said signalling unit may be integrated into the inhalation device itself and / or is part of an external entity . A more elaborate example of the signalling unit is an electronic display device , but also embraces simpler lights , speakers and / or vibrators . The first signal may be a single signal of a single type but could also be a signal sequence combined of various different signal types . Likewise , the second or third or fourth signal may be a single signal or can also be a signal sequence . Preferably, the first signal , the second signal , the third signal and the fourth signal are distinguishable and different from each other, such that the user / patient can readily identify the different meanings of the signals and different scenarios encountered during an ongoing inhalation process . The first signal , the second signal and the third signal are representative of or part of an inhalation process / breath guidance or feedback function provided by the present procedure and devices . Said inhalation process / breath guidance may be limited to only one of the first signal , the second signal and the third signal , but can also include more detailed information, for example , in graphical or written or voice form to be output by the signalling unit .

[0026] The operation method according to the present disclosure and invention, in particular the one outlined above , epitomizes a number of relevant and desired functionalities . One of said functionalities is the output of a bespoke signal , for example , the first signal in a case whenever the monitoring of an ongoing inhalation process indicates that one or more pertinent inhalation parameters have underrun or exceeded a related first pre-set threshold value for said one or more pertinent inhalation parameters . "Pre-set" here means that the threshold value is set and embodied in the procedures and devices before an inhalation process to be monitored is started . Optionally, the threshold values may experience dynamic adaption during the inhalation process . The parameter monitoring is done consistently throughout an ongoing inhalation process and thus implies that the bespoke signal may be output several times throughout the ongoing inhalation process . The first threshold value is a parametric value that is representative of the borderline between the inhalation process parameters being optimal or non- optimal . Depending on the individual inhalation process parameters underrunning or exceeding the threshold value means that the inhalation parameters fall into a non-optimal range and that inhalation is thus not performed optimally with respect thereto . The user / patient is accordingly informed by the output of the first signal and could then counteract . The first signal can basically be seen as a first information or even an alarm for the user / patient or the accompanying physician or caregiver that the inhalation process is non-optimal . The second signal is output in cases where a second pre-set threshold value of one or more inhalation process parameters is underrun or exceeded, wherein said second pre-set threshold value is different to the first one and indicative of a worsening of the inhalation process . Preferably, the second pre-set threshold value is numerically located "deeper" within a non-optimal inhalation process parameter realm . Accordingly, the second signal is output to the user / patient indicating that the quality of the ongoing inhalation process has worsened . Like the first signal , the second signal can also be considered to be an information or even alarm for the user / patient or the accompanying physician or caregiver that the inhalation process is non-optimal , but with an increased degree of urgency . In essence , the first signal and the second signal form a signal , information and / or preferably alarm cascade , wherein the first signal is issued at the onset of an ongoing inhalation process developing non-optimally, the second signal is a more assertive signal , information or preferably alarm that indicates that the quality of the inhalation process has worsened as compared to a stage in the inhalation process where the first signal was output . Described differently, if a user / patient of a medical inhalation device started performing the inhalation process in a non-optimal way, then first the first signal is issued as an initial information or alarm . If and whenever the user / patient does not improve the inhalation process and the respective inhalation process parameters worsen then the second signal is output indicating to a user / patient that there is a certain need and urgency for improving the inhalation process with respect to one or more pertinent inhalation proces s parameters .

[0027] In addition to the above scenario , where the first signal and the second signal represent a worsening of the inhalation process , the present disclosure and invention optionally also embraces that the first signal and the second signal are simple indicators of the degree that a pre-set threshold value is underrun or exceeded . A low degree of deviation, i . e . , a deviation from the first pre-set threshold value will be notified by the first signal . A higher degree of deviation, i . e . , a deviation from the second pre-set threshold value will be notified by the second signal . Hence , the signal output depends on the degree of deviation from an inhalation process parameter threshold that separates optimal and non-optimal inhalation .

[0028] The s killed reader will naturally understand that the signals and signal outputs are preferably finite and not continuous , which means that they will inform / alert the user / patient and then switch off but can also be continuous . The dif ferent options may depend on the signalling device . However, the underlying pertinent inhalation process parameters will be continuously monitored during the ongoing inhalation process and if the pre-set threshold values will be underrun or exceeded again, then the respective signals will be output again or, if continuous , maintained . Preferably, only the first signal is output if and whenever the user / patient does not underrun or exceed the second pre-set threshold value . Practically, this means if the user / patient is starting to perform the inhalation process non-optimally, but then stays stable in said non-optimal stage or even improves it , the second signal does not need to be output since no further worsening to the degree that the second preset threshold value is underrun or exceeded occurs . So basically, the first signal and the second signal preferably represent different notification or alarm levels depending on how far a pertinent inhalation process parameter is outside the optimal range . A yet further optional functionality of the operation method is the output of a versatile third signal that preferably continuously provides information about the ongoing inhalation process . Unlike the first signal and the second signal that could be seen to be finite signals that only occur under certain conditions , the third signal could be construed to be an informational signal that allows a user / patient to be informed live about one or more pertinent inhalation process parameters as they evolve throughout the ongoing inhalation process . In other words , the third signal continuously informs the user / patient about the specifics and the quality of an ongoing inhalation process .

[0029] A wide range of possible signals outputs by the signalling unit is conceivable and part of the present disclosure and invention . For example , such signals may range from simple and different light signals output directly on or through the inhalation device but may also embrace elaborate graphical information or voice information output by an external signalling unit , for example , when implemented in an external electronic device like a smartphone or tablet computer . In the latter case , it is conceivable that there is detailed information related to the ongoing inhalation process and its parameters are output to provide the user / patient or the physician or caregiver with a detailed account of the ongoing inhalation process . Naturally, the information provided can then form the basis for improving the ongoing inhalation processes by instructing the user / patient what to do in order to improve the ongoing inhalation process . Preferably, in the present invention and disclosure , the first signal and the second signal form a functional unit and are interrelated, whereas the third signal may occur unrelated to and independent from the first signal and the second signal . The respective "and / or" connection used above and in original claim 1 do exactly indicate this .

[0030] Finally, it is noted that the above and herein below defined operation method relates to the intrinsic functionalities of an inhalation device or components of an inhalation device system . Said operation method is thus preferably independent from an actual inhalation process to be carried out by a user / patient . Thus , the operation method represents a non-therapeutic , non-diagnostic and non-surgical method of operating an inhalation device and thus optionally does not relate to methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body .

[0031] In the above method, the first signal is a first vibration signal and / or a first light signal and the second signal is a combination of a second vibration signal that is stronger or different to the first vibration signal and a second light signal that is different to the first light signal .

[0032] The above is a non-exclusive example of how the above-mentioned signal cascade of the first signal and the second signal may look like in practice . The first signal , i . e . , the first alarm signal can be a first vibration signal on its own or in combination with the first light signal . The second signal is then preferably a combination of a second vibration signal that is distinguishable by the user / patient from the first vibration signal and the second light signal that is different from the first light signal . Hence , it is conceivable that the first signal is a "gentle" signal making the user / patient aware that one inhalation process parameter is becoming non-optimal . The second signal is then a more assertive signal that makes the user / patient aware that one or more pertinent inhalation process parameters have become increasingly non-optimal , i . e . , worsened with respect to the situation when the first signal was output . It is conceivable and embraced in the present disclosure and invention that the first signal and the second signal and the respective signal cascade can be a combination of any conceivable and suitable signals perceivable by the user / patient . The above example is thus non-limiting . Accordingly, the following signal cascades are also embraced : an optical signal in a first colour and an optical signal in a second colour optionally each in combination with vibration signals , a first vibration signal and a different second vibration signal only, a first combination of a vibration and / or light and / or sound signal and a second combination of a vibration and / or light and / or sound signal .

[0033] Preferably the above method further comprises generating and sending a control signal to the signalling unit , wherein in response to said control signal , the signalling unit outputs a fourth signal if and whenever the inhalation device is not ready for use .

[0034] This represents an additional functionality of the operating method of the inhalation device , wherein the suitable signal is output and indicates when the inhalation device is not ready for use . This is advantageous in alerting and informing the user about a non-operable state of the inhalation device and potentially errors that need to be mended before use . Preferably, if said fourth signal is not output , then the user / patient may assume an operable state of the inhalation device and commence or continue the inhalation process . As already explained above but also as further explained herein below, said fourth signal can be of any type and any nature as long as it is suitably perceivable by the user / patient . One nonlimiting example is the output of a yellow or red light on the housing of the inhalation device itself .

[0035] In the operating method according to the present disclosure and invention, preferably the signalling unit outputs the first signal if and whenever the first pre-set threshold value of an inhalation process parameter is exceeded during the inhalation process and outputs the second signal if and whenever the second pre-set threshold value of an inhalation process parameter, that is higher than the first pre-set threshold value , is exceeded during the inhalation process . This optional scenario relates to cases where pertinent inhalation process parameters should be limited with respect to an upper level that is indicative of a non-optimal inhalation process . In such cases , a first pre-set threshold value exists that if exceeded represents the onset of a non-optimal inhalation process . Accordingly, the first signal is output . There is then a second preset threshold value that is higher than the first pre-set threshold value and if said value is exceeded, then this is indicative of a further worsening of the inhalation process with respect to that inhalation process parameters . Consequently, the second signal is output to indicate the growing deterioration of the inhalation process prompting the user / patient to counteract accordingly . Optionally and as explained above , the first signal and the second signal may also be indicative of the degree of deviation from a threshold value . The signal output thus depends on how strongly the threshold value is exceeded . A small exceedance triggers the first signal and a larger exceedance then triggers the second signal .

[0036] One non-limiting preferred example of the above scenario is a case where the inhalation process parameter is the breath flow rate ( also referred to as inspiratory flow rate herein ) and / or the tidal volume ( also referred to as inhaled volume ) during the inhalation process , and optionally wherein the first pre-set threshold value of the breath flow rate is in the range of 30 1 / min or more , preferably 40 1 / min or more to less than 75 1 / min and the second pre-set threshold of the breath flow rate is 75 1 / min or more .

[0037] In this example of the operation method, the ongoing inhalation process is monitored with respect to the breath flow rate during the inhalation process . If the value of the breath flow rate exceeds the first pre-set threshold value of 30 1 / min then the first signal is output as a first information or alarm indicating to the user / patient that the inhalation process is on the onset of becoming non-optimal . Depending on the capabilities of the signalling unit , the user / patient may be directly informed that specifically the breath flow rate is excessive . If the user / patient does not counteract and the inhalation process worsens with respect to the breath flow rate and consequently the second pre-set threshold value of 75 1 / min is exceeded, then the second signal is output informing or alerting the user that there is an urgency in improving the ongoing inhalation process . The s killed reader will readily understand that using the breath flow rate or the tidal volume are j ust two of many possible examples of inhalation process parameters that could be taken into account when issuing the first , second or third signal in the context of the present operation method . The s killed reader will also understand that for certain inhalation process parameters , exceeding upper limits is not crucial , but underrunning lower limits thereof is . In such scenarios the first signal is output if and whenever a first critical threshold value is underrun, meaning that the value of the respective inhalation process parameter is too low . If said value decreases even further and thus underruns the second pre-set threshold value , the second signal is output . A non-limiting example thereof is the tidal volume that can be monitored and considered and a significant pre-set threshold value is 1 liter . If said value is underrun, the user / patient is alerted via a respective signal output and instructed to take deeper breaths through the inhalation device .

[0038] It is further optionally embraced that the respective pre-set threshold values are user-specific and are pre-set according to the inhalation specifics of a user / patient . For example , for users / patients who naturally have a high default breath flow rate , the threshold values are set higher than for users / patients that naturally have lower default breath f low rates . This way it can be avoided that the first or second signal is issued inflationary, but instead only when user / patient-specif ic threshold values are underrun or exceeded .

[0039] A further concept of the present invention and disclosure is that the pre-set threshold values are not fixed through the inhalation process but can be changed and adapted during the inhalation process . For example , the first pre-set threshold value and / or the second threshold value at the beginning of the inhalation process may have different values as compared to the middle or the end of the inhalation process . Hence , in particular the first and second signal are then output according to different preconditions at different times during the inhalation process . This may be used for example to adj ust the feedback to a reasonable threshold value depending on the current / daily state of lung health, motivation and or wellbeing of the user / patient to allow him to optimize his inhalation in the range within his capabilities and not to frustrate or demotivate the patient / user .

[0040] In the above and herein described operation method, preferably the signalling unit comprises or consists of any one of the following : means to generate an optical signal ; preferably a light signal , means to produce an acoustic signal ; preferably a sound and / or a voice signal , means to produce a tactile signal ; preferably a vibration signal and an electronic display device .

[0041] It is thus further part of the present disclosure and invention that in the here described methods , processes and systems , a variety of means are conceivable for the signalling unit . Embraced are basically all technical means and hardware that are capable and configured to output signals that are perceivable by humans . These means can also be freely combined in order to output any conceivable signal sequence or signal cascade that can comprise any one of optical signals , acoustic signals and haptic signals .

[0042] In one option of the present disclosure and invention, the signalling unit is implemented in the inhalation device itself .

[0043] In such a case , the signalling unit is an integral part of the inhalation device itself and thus integrated therein . This in turn implies that the inhalation device itself outputs respective signals and feedback information via the signalling unit comprised therein . For that purpose , the inhalation device itself embraces any suitable hardware means for outputting such signals and information . This has the advantage that the user / patient has a single device with which an inhalation process is performed and that at the same time provides inhalation process feedback and guidance information . For example , the inhalation device may comprise as the signalling unit one or more light sources , for example LEDs that produce light signals representative of the first signal and the second signal or a vibrator that produces a tactile signal .

[0044] Based on the above option of having the signalling unit being part of the inhalation device itself , it is preferred that the first signal is a first vibration signal of the inhalation device and / or a first light signal from the inhalation device and that the second signal is a combination of a second vibration signal of the inhalation device that is stronger or different to the first vibration and a second light signal from the inhalation device that is different or identical to the first light signal , optionally wherein the first and the second light signals are output from a top part of the inhalation device , which is made of translucent material through which the light signals are emitted .

[0045] This further option underlines that in scenarios where the signalling unit is part of the inhalation device , a versatile number of signals , signal combinations and signal cascades may emanate from the inhalation device itself , which contains the respective means for generating such signals . The inhalation device itself thus conveys the respective information content directly to the user / patient .

[0046] A further related option in cases where the signalling unit as part of the inhalation device preferably embraces that the fourth signal is a combination of a third vibration signal of the inhalation device and a sound signal from the inhalation device .

[0047] Accordingly, as above , the s killed reader will readily understand that also , for example , the fourth signal can be output and emanated in various suitable forms from the inhalation device itself to convey the respective information content directly to the user / patient . It is especially beneficial to emit such inhalation device status signal also on the device itself , such that a user / patient recognizes it directly in connection with the device itself .

[0048] Another option embraced by the present disclosure and invention is that the signalling unit is implemented in a device different from and external to the inhalation device , preferably in an electronic device further preferably with a computer program stored on the electronic device configured to generate a graphical user interface for outputting data of the inhalation process .

[0049] In such a case , the respective signals are output and the respective information or alarms and inhalation process / breath guidance are provided on a device that is not the inhalation device itself , but a device separate and external thereto . Preferably envisaged are external electronic devices like mobile phones , smartphones , tablet- and mobile computers and any kind of smart personal electronic devices . All of the devices commonly include electronic display devices , processors and suitable computer programs that enable said devices to output information including the first and second signal , but also additional optional information on the inhalation process . For example , it is inconceivable that on the display devices of the aforementioned electronic devices inhalation process / breath guidance is provided by suitable graphical and / or written information . Also conceivable is a respective output in the form of sound or voice via suitable hardware means related to the electronic- or electronic display device . In principle , inhalation process / breath guidance can be provided by all types of human-perceivable signals that the respective electronic devices can generate .

[0050] As part of the present disclosure and invention it is also foreseen that the above options of having an integral and nonintegral , i . e . , external signalling unit are combinable or combined . For example , it is surely embraced herein that on the one hand the inhalation device itself provides a basic inhalation process / breath guidance , whereas the signalling unit in from of or as part of an external electrical device additionally provides the inhalation process / breath guidance in the same or in a different form and even further details . The latter is due to the fact that the aforementioned electronic devices normally have larger and more versatile signal output capabilities than the ones that could be incorporated within the inhalation device itself . In other words , the signalling unit may optionally be part of the inhalation device and the external device and thus outputs the respective signals on said both devices . Basically, this would imply the provision of two or more signalling devices or one signalling device with two or more sub-units . Finally, it is clear that for the above option where the signalling unit is an external unit that respective technical means are present that allow the exchange of data between the sensing unit , the control unit and the signalling unit irrespectively from where they are located and implemented . All technical means conceivable by the s killed person for said purpose are embraced here .

[0051] As an option related to the above case of an external signalling unit , the signalling unit is preferably an electronic display device and the method further comprises : that in response to said control signal and during the inhalation process , the electronic display device outputs , preferably as the third signal , graphically and / or numerically and / or in writing and / or in spoken text at least one of the group of information consisting of : breath pattern, breath flow rate , peak flow rate , regularity of breathing cycle duration, tidal volume , inhalation / exhalation ratio , respiratory minute volume , breathing frequency, breathing durations , breath pauses , live inhalation feedback information and instructions on how to optimize the ongoing inhalation process , wherein the displayed information is to inform a user of the inhalation device about the quality of the inhalation process and to trigger improvements of the inhalation process , and optionally the displaying of information is adj usted or stopped or suspended if and whenever a user of the inhalation device cannot abide to improve the inhalation process . Further optionally, the displaying of information is sorted according to the most important to the least important inhalation process parameters to be changed or improved . As it can be appreciated from the above outlined optional aspects of the present operation method, in particular when an external signalling unit is outputting the respective signals , a large number of additional functionalities of the operation method are conceivable . For example , the values of various different inhalation process parameters as listed above can be continuously displayed so as to give the user / patient or an accompanying physician or caregiver live insights into the ongoing inhalation process . Related to said live output , the operation method may further comprise the output of additional information for the user / patient how to improve the ongoing inhalation process with respect to one or more relevant inhalation process parameters . Hence , the user / patient is basically given specific proposals and recommendations on how to improve the ongoing inhalation process . The user / patient is thus further given the chance to improve the inhalation process as it occurs and as it is ongoing . However , as the s killed reader may appreciate , a user / patient may not always be able or willing to follow such instructions due to his individual state of disease or due to his daily wellbeing or due to his emotional and / or mental state or due to his cognitive capabilities and to improve an ongoing inhalation process . In such cases a continuous output of notifications , information or alarms or relevant live data and improvement instructions may become frustrating for the user / patient . Consequently, it is also embraced by the present disclosure and invention that respective signal outputs are muted, suspended or completely stopped if the user / patient is not in a position to improve the ongoing inhalation process with respect to one or more pertinent inhalation process parameters . The s killed reader will appreciate that this functionality is based on a continuous monitoring of the inhalation process and in particular relating to the fact that threshold values for certain inhalation parameters are underrun or exceeded with potential changes in inhalation behaviour of a user / patient . If during an ongoing non-optimal inhalation process the monitoring yields that for a certain amount of time the user / patient is not able to improve the inhalation process , then the respective signal outputs are muted, stopped or suspended . In the above case , the information output by the optional electronic device or electronic display device are part of or constitute the third signal . Alternatively, in such a situation, the pre-set threshold values can be adapted to adj ust to the user' s / patient' s daily status . In an alternative example , the thresholds are adapted stepwise while monitoring and guiding the user / patient to consider a stepwise guiding towards an optimal inhalation manoeuvre .

[0052] Said further examples of the present disclosure and invention highlight again that in particular in the case where the signalling unit is an external unit and the signal output is performed on said external unit which is preferably an electronic device and more preferably an electronic display device , the degrees of freedom of the signals output are thus high . Hence , the various signals outlined herein can be elaborate signals and clearly go beyond simple light or sound signals and can basically embrace any suitable information output within the technical capabilities of an electronic display device or more generally an electronic device including an electronic display device but also including respective other signal devices , for example standard light devices .

[0053] The above listed inhalation process parameters represent parameters that the sensing unit is configured to measure and monitor and are in line with the s killed person' s common technical understanding of the respective terminologies used . Based on one or more of said parameters , the above-described inhalation process and breath guiding is generated and given . It is embraced by the present disclosure and invention that one or more or all of the aboveindicated parameters can be considered in the process of evaluating the quality of an ongoing inhalation process and outputting the respective signals and inhalation process information and guidance . Also , for each of said inhalation process parameters individual preset threshold values may be selected that then in turn determine the output scenarios in particular for the first signal and the second signal . Especially for the output on or via an external electronic device where there are more possibilities of displaying output information, a selection of which parameters are to be guided first can be implemented to first guide the user / patient on the most important parameter and when this parameter is below / above the preset threshold value , the next parameter can be guided to stepwise lead the patient / user to an optimal breathing manoeuvre / process during his inhalation .

[0054] It can also be considered to implement positive feedback on such an electronic device , if the user / patient was successful in performing his / her inhalation within the pre-set thresholds and also to give positive feedback when he / she managed to change his inhalation process and do it within the pre-set threshold values after he was informed about being above the pre-set threshold values .

[0055] In line with the above outlined additional functionalities , it is preferred that the first signal and the second signal inform the user / patient of the inhalation device about a non-optimal inhalation process and trigger improvements of the inhalation process , and / or the first signal and the second signal are stopped or adj usted, muted or suspended if a user of the inhalation device cannot abide to improve the inhalation process .

[0056] This option basically epitomizes the technical concepts and functionalities already described herein above and underlines that in particular the first signal and the second s ignal could be seen to be signals that inform or alert the user / patient about a non- optimal inhalation process . Said signals could then also prompt the user / patient to initiate means for improving the ongoing inhalation process . Should the user / patient not be in the position for that or unwilling to do so , the respective signals can be stopped, adapted, muted or suspended in order not to frustrate , annoy or unsettle the user / patient .

[0057] In addition, the present invention and disclosure embrace the concept of a dynamic and continuous breath guiding , where the guiding functionality may be adj usted based on changes during an inhalation process in order to preferably successively and iteratively optimise the inhalation process which thus becomes a continued and guided human-machine interaction process . This may embrace adapting preset ranges during the inhalation process dynamically and for each user / patient individually . For example , if the user / patient is given a first breath guidance during an inhalation process , the user' s / patient ' s reaction thereto is measured and monitored . If an improvement in the inhalation process is detected, then the user / patient may be guided, for example , by an appropriate action at a graphical , acoustic, and / or tactible user interface to continue via a respective signal output by the signalling device . The detected improvement may then also be taken as a basis to yet further improve the same and / or another inhalation process parameter even further to thereby iteratively lead the user / patient to an optimal inhalation process altogether . Similarly, if no or a too small improvement is detected, the breath guiding will also be continued and the continued breath guidance given optionally adapted to the capabilities of the user / patient . For example , the user / patient may not be physically able to sufficiently implement the initial breath guidance given, for instance , if the recommended change is too significant and demanding , or if there are other measurable user / patient actions , such a coughing (being detectable via an audio detection device such as a microphone ) , which prevent the user from inhaling at a prescribed ( therapeutic ) protocol . In such a case , the initial breath guidance of the dynamic and continuous breath guiding may be adapted to the individual (physical ) capabilities and present conditions of the user / patient to make it easier for her or him to follow and successfully implement the breath guidance . This could be done , for example , by selecting smaller steps and increments for changing one or more inhalation process parameter .

[0058] The inventors have found in experiments that providing breath guidance during an inhalation process according to the method of the present invention and disclosure brings significant advantages as compared to inhalation processes without guidance . Most significantly, it was found that in the course of providing continued breath guidance , the breathing patterns became more regular ( less variable ) and reproducible . In addition, all of the pertinent inhalation process parameters : average maximal / peak flow - which was positively reduced, average inhale / exhale ratio - which was positively increased, breath duration - which was positively increased and the tidal volume improved when applying breath guiding . For example , the continued breath guidance supports a reduction of the peak flow rate on average by about 36 to 38 % and the inhale / exhale ratio by about 27 % thus shortening the overall treatment time in a similar manner . This was in particular the case when using a mobile device ( such as a smartphone , a tablet device or the like ) being configured as a control device ( also referred to as "signalling unit" herein) by a software application program ( referred to as "APP" ) to continuously provide user signals and thereby continued breath guidance to appropriately interact with the inhalation device . Together , this leads synergistically to more efficient inhalation processes with better use of medications , better treatment quality and lower variations in delivered doses and shorter, more focussed inhalation processes saving the user / patient time and improving the therapeutic prospects .

[0059] A further important global aspect of the present disclosure and invention is an inhalation device itself comprising : a sensing unit configured to monitor an inhalation process and to measure and collect data of and during the inhalation process , a signalling unit configured to output a signal , preferably an optical , acoustic and / or a tactile signal , a control unit configured to receive and process the data collected by the sens ing unit and to control the signalling unit based on said data, wherein the control unit is further configured to control the signalling unit such that the signalling unit outputs a first signal if and whenever a first preset threshold value of an inhalation process parameter is underrun or exceeded during the inhalation process and outputs a second signal if and whenever a second pre-set threshold value of an inhalation process parameter , that is different from the first pre-set threshold value , is underrun or exceeded during the inhalation process . The "first signal" and "second signal" are preferably the "first signal" and the "second signal" of the above operation method .

[0060] Optionally, the above defined inhalation device is the inhalation device used in the methods and procedures according to the present disclosure and invention, preferably the above operation method . In particular so for the scenario where a signalling unit is incorporated in the inhalation device itself . As it can be appreciated from the above defined inhalation device , preferably all of the respective components , namely the sensing unit , the control unit and the signalling unit are part of the inhalation device itself and comprised therein . Consequently, the inhalation device itself is configured and capable to generate and output the first and the second signal and to provide at least basic inhalation process / breath guidance . Furthermore , if the methods and procedures according to the present disclosure and invention are carried out using the above defined inhalation device , the respective signal output is performed by the inhalation device itself . Basically and optimally, the inhalation device defined herein provides the hardware basis or hardware equivalent of the operation method previously outlined . Consequently, similar and related hardware features are thus found with respect to the present inhalation device and comprise the following ones outlined below, which are preferably mutually combinable . Thereby, the inhalation device embodies the same functionalities and technical advantages that have been explained and outlined above for the operation method .

[0061] In one preferred embodiment of the inhalation device the first signal is a first vibration signal of the inhalation device and / or a first light signal and the second signal is a combination of a second vibration signal of the inhalation device that is stronger or different to the f irst vibration and a second light signal from the inhalation device , optionally wherein the first and the second light signals come from a top part of the inhalation device , which is made of translucent material through which the light signals are emitted . This option is analogous to the above-described option for the operating method and the explanations provided there apply mutatis mutandis here .

[0062] In a yet further preferred embodiment of the inhalation device , the control unit is further configured to control the signalling unit such that the signalling unit outputs the first s ignal if and whenever the first pre-set threshold value of an inhalation process parameter is exceeded during the inhalation and outputs the second signal if and whenever the second pre-set threshold value of an inhalation process parameter, that is higher than the first pre-set threshold value , is exceeded during the inhalation . This option is also analogous to the above-described option for the operating method and the explanations provided there apply mutatis mutandis here .

[0063] Optionally, in the inhalation device the inhalation process parameter is the breath flow rate and optionally the tidal volume , and optionally wherein the first pre-set threshold of the breath flow rate is in the range of 30 1 / min or more preferably 40 1 / min or more to less than 75 1 / min and the second pre-set threshold of the breath flow rate is 75 1 / min or more . This option is analogous to the above-described option for the operating method and the explanations provided there apply mutatis mutandis here .

[0064] Yet further optionally, in the inhalation device the control unit is further configured to control the signalling unit to output a third signal if and whenever the inhalation device is not ready for use , optionally wherein the third signal is a combination of a third vibration signal of the inhalation device and a sound signal from the inhalation device . This option is analogous to the abovedescribed option for the operating method and the explanations provided there apply mutatis mutandis here . The "third signal" here equals the "fourth signal" of the above operation method .

[0065] Finally, it is further optional that in the inhalation device the signalling unit comprises or consists of any one of the following accommodated within the inhalation device : means to generate an optical signal ; preferably a light signal , means to produce an acoustic signal ; preferably a sound signal and / or a voice signal , means to produce a tactile signal ; preferably a vibration signal and an electronic display device . This option is also analogous to the above-described option for the operating method and the explanations provided there apply mutatis mutandis here .

[0066] A yet further important aspect of the present disclosure and invention is an inhalation device system, comprising : an inhalation device , an electronic device that is different from and separate to the inhalation device , preferably a mobile phone , smartphone , smart watch, smart personal device or tablet computer , wherein both the inhalation device and the electronic device comprise communication means configured to establish a wired or wireless communication connection between the inhalation device and the electronic device to exchange data on an inhalation process performed with the inhalation device ideally in near to real time .

[0067] Optionally, the above defined inhalation device system comprises a medical inhalation device and preferably the inhalation device that has been outlined herein above . Yet further optionally, the above-defined inhalation device system is a device-related representation of the above described option of having the signalling unit external to the inhalation device itself . Also , all of the above outlined and explained interrelations , functionalities and technical advantages and benefits apply mutatis mutandis to the inhalation device system and will not be repeated here for the sake of conciseness . The present inhalation device system basically represents a pairing of an inhalation device with which the respiratory treatment , i . e . , the inhalation process is performed and an external electronic device that are mutually configured to communicate with each other, such that inhalation process / breath guiding can be provided also on said electronic device . The technical means to allow such mutual communication are the ones that are known to the s killed person and embrace wired and wireless communication means , like data-transf er cables , Bluetooth, NFC or Wi-Fi hardware or the like . As part of the present disclosure and invention and preferably in the context of the present inhalation device system, it is also conceivable that the first to fourth signal and / or inhalation process / breath guidance is provided by means of e-mail or push-notification handled by the external electronic device .

[0068] The present disclosure and invention is not limited to the above defined methods and procedures of operating an inhalation device . The present disclosure and optionally the present invention also include an inhalation process in relation thereto . Said inhalation process comprises the following steps : performing an inhalation process preferably to prevent or treat a respiratory disease or malfunction but also for wellbeing and prophylaxis , using an inhalation device , monitoring the ongoing inhalation process with respect to pertinent inhalation process parameters and features and collecting respective data, evaluating the inhalation process based on the monitoring results and the data obtained and collected during the inhalation process and outputting inhalation process information that inform the user / patient and or a physician or caregiver about the current / live quality of the inhalation process via suitable signals constituting the inhalation process information and optionally issuing notifications or alarms if and whenever relevant inhalation process parameters are indicative of a non-optimal inhalation process . Optionally, the notifications , information or alarms can be provided in a cascading / manner where the assertiveness of the notifications , information and alarms is increased as the inhalation process further deviates from an optimal inhalation process , i . e . , worsens . Optionally, the inhalation process comprises the output of inhalation process / breath guidance information, which is bespoke information that is issued in response to the monitoring results and the alarms or notifications , information or alarms output to provide the user / patient with recommendations how to improve the ongoing inhalation process . Hence , the user / patient is basically accompanied in his or her inhalation process and given live information on the one hand with respect to basic information of the inhalation process but also in particular with information in case the inhalation process is becoming the non-optimal . In the latter case , not only will the user / patient be informed or alerted, but he or she is also incited to carry out certain actions to improve the ongoing inhalation process . Should the user / patient not be able or willing to improve the inhalation process accordingly, then optionally the respective alarms , notification or information can be stopped or suspended or muted or the parameter threshold values adj usted . This innovative inhalation process procedure basically guides the user / patient using a medical inhalation device through the inhalation process to ensure that inhalation process is performed as good as possible and to trigger means to improve an inhalation process that becomes non-optimal . This way the inhalation process quality can be greatly improved, thus the therapy success is increased and the user / patient experience improved in that the user / patient is not left alone doing inhalation process but guided throughout which improves the user / patient ' s confidence and satisfaction when performing the inhalation process and using the medical inhalation device .

[0069] A yet further aspect of the present disclosure and invention is a computer program that is configured to facilitate the herein described methods and procedures . Specifically embraced is a computer program or app , respectively one that is to be executed on respective means , i . e . , computer processors of the inhalation device itself , but preferably of the external electronic device and configured to output the described signals , information and inhalation process / breath guidance in any suitable form and in different degrees of detail . More specifically, the computer program is configured to output the inhalation process / breath guiding information on an electronic display device in graphical form, for instance via generating a suitable graphical user interface , also in line with the examples given above and herein below . Further embraced is a computer-readable storage medium on which the above computer program is stored and yet further a carrier containing the computer program, wherein the carrier is one of an electrical signal , optical signal , radio signal or computer-readable storage medium.

[0070] Fig. 1 shows a control device 20 according to an example and embodiment of the present disclosure and invention in combination and communication interaction with an aerosol nebulizer system 30. Here, the control device 20 may be a mobile device, a smartphone, a tablet, a wearable device, or the like. Preferably, the control device 20 is in the device for providing continued breath guidance according to the present disclosure and invention. The aerosol nebulizer system 30 therein is preferably an example of the "inhalation device" of this disclosure and invention.

[0071] Further, the aerosol nebulizer system 30 may comprise an aerosol generator 31. Here, the aerosol generator 31 may generate aerosol for a specific extended period of time, for example during an inhalation of the user, preferably triggered by a breathing sensor. The aerosol generator 31 may also be triggered to stop generating aerosol during an exhalation phase. The aerosol generator 31 may be a nebulizer, an atomizer, a humidifier, a pneumatic nebulizer, an electronic nebulizer, an ultrasonic nebulizer, an electro-hydrodynamic nebulizer, an electrostatic nebulizer, a jet nebulizer, a humidifier-nebulizer for ventilation devices. Preferably the aerosol generator is a membrane nebulizer, more preferably a vibrating membrane nebulizer, e.g. an electronic vibrating membrane nebulizer.

[0072] In particular, the aerosol generator may be an electronic nebulizer, e.g. a piezo-electrically driven nebulizer, i.e. a nebulizer driven by a piezo-electric element. The aerosol generator may be a vibrating membrane nebulizer, such as those disclosed in EP-A-2 030 644, US-A-2012 / 0085344 and US-A-2013 / 0112197 , the contents of which are hereby incorporated herein by reference in their entirety.

[0073] The aerosol generator may be a continuous aerosol generator, e.g. a continuously operated nebulizer, for example during an inhalation by the user. In particular, the aerosol generator may be a vibrating membrane nebulizer, e.g. a vibrating membrane nebulizer with a mixing chamber or aerosol chamber. The mixing chamber may have an inhalation valve that allows ambient air to flow into the mixing chamber during an inhalation phase, while preventing aerosol from escaping during an exhalation phase . Further, the mixing chamber may have an exhalation valve that allows discharge of the patient ' s respiratory air during the exhalation phase , while preventing an inflow of ambient air during the inhalation phase .

[0074] The aerosol generator may allow for aerosol losses occurring during exhalation of a regularly breathing user or patient to be minimized like described in US-A-2006 / 0054166 . The aerosol generator may produce an aerosol continuously .

[0075] The exhalation valve may ensure that the patient ' s exhaled air is vented to the surroundings without significantly reaching the mixing chamber . During the exhalation phase , the continuously operating aerosol generator may accumulate or concentrate the aerosol in the mixing chamber, so that during an inhalation phase not only the amount of aerosol generated due to the continuous production is available for the inhalation, but at the beginning of the inhalation phase an aerosol bolus can be inhaled, which is available because of aerosol accumulation during the exhalation phase . Nebulizers adopting such an approach are also disclosed in EP-A-1 927 373 and US-A-2012 / 0037154 , which are incorporated herein by reference .

[0076] The aerosol generator , as described, is suitable to nebulize a liquid, which is held in a reservoir ( not shown ) of the aerosol nebulizer system 30 . The liquid may be a fluid that contains at least one active pharmaceutical ingredient , medical drug and / or at least one therapy relevant fluid ( such as a sodium chloride solution ) , and / or a fluid from which an aerosol is generated for the purpose of assisted diagnosis ( such as a fluorescent aerosol , a mono-disperse aerosol , or the like ) . The liquid / fluid is transformed into an aerosol by the aerosol generator 31 , which subsequently enters e . g . a mixing chamber 34 that is connected to a mouthpiece 35 . From the mouthpiece , the patient / user inhales the aerosol into the respiratory tract , like lung , throat , nose or sinuses , to perform a medical treatment according to a prescribed aerosol therapy protocol . Further, the aerosol generator 31 ( Fig . 1 ) operates according to configuration data that may be provided from the control device 20 via a communication interface 33 or may be pre-set at a processing unit 32 of the aerosol nebulizer system 30 . Conversely, the aerosol nebulizer system 30 transmits ( first data transmission) usage data via the established wireless communication connection to the control device 20 . The usage data of the aerosol nebulizer system may include one or more data sets and, in particular , one or more data sets of sensor data ( generated by one or more sensor units 38a , 38b , 38c, 38d, 38e at or near the aerosol nebulizer system 30 ) , status data ( e . g . indicating an operation status of one or more components of the aerosol nebulizer system 30 , indicating a charging state or charging operation of a battery of the aerosol nebulizer system 30 ) , and / or user data ( e . g . indicating a user identification ) .

[0077] Here , the wireless communication connection may be one of a Bluetooth connection, a Bluetooth Low Energy connection, a near field connection, a WiFi or WLAN connection, an infrared connection, a LoRa connection ( a low power wide area network connection intended for wireless battery-operated Internet of things devices ) , a radio connection such as LTE , 5G, or the like . The data rate of Bluetooth Low Energy, for example , may be lower than 200 kBit / s , or even lower than 100 kBit / s . In addition, a wireless LoRa connection may have a data rate as low as 0 . 3 - 50 kBit / s .

[0078] Here , using the above radio connection, the aerosol nebulizer system 30 may also directly communicate with a server as the control device 20 to transmit the configuration data and / or usage data . In such a scenario , the server may operate as the control device 20 .

[0079] For establishing the wireless communication connection, the control device 20 (mobile device ) may be provided with a communication unit 21 and the aerosol nebulizer system 30 may be provided with the communication interface 33 , as shown in Fig . 1 . It is emphasized here that the wireless communication connection to the control device 20 is preferably established continuously to ensure the continued breath guiding during the inhalation session . According to an embodiment , the device 20 illustrated in Fig. 1 may be suitable and configured for providing a continued breath guidance when using the aerosol nebulizer system 30 during an inhalation session . As explained, the aerosol nebulizer system 30 comprises an aerosol generator 31 for nebulizing a liquid or an aerosol source for dispensing aerosol . The continued breath guidance may be provided for the inhalation session which comprises a plurality of inhalations and exhalations of a user or patient in respective sequence . For example , a therapy protocol may be set according to which the user should inhale a specific medication for an extended period of time , such as 2 minutes or the like , which include a plurality of inhalations and exhalations . As there may be significant variations in the amount of air intake , air flow, duration between individual inhalations and exhalations , for example for a user which exhibits a medical condition, or because a user typically may have to adj ust to the operation of the inhalation device , the device 20 is adapted to provide continued guidance as to an improved process of how the user interacts with the inhalation device .

[0080] The device 20 may comprise a communication unit 21 which is configured to establish a wireless communication connection and to perform data transmission with the aerosol nebulizer system 30 . Here , the data transmission may include inhalation data (usage data, as explained above ) of a plurality of inhalations and exhalations of a user during the inhalation session .

[0081] The control unit 22 of the control device , for example a microprocessor , a controller, or the like , may be configured to , during the inhalation session, continuously and in real-time , i . e . during a plurality of inhalations and exhalations , determine , as a first determination, whether a tidal volume (which may also be referred to as an inhaled volume herein) for a respective inhalation of the plurality of inhalations is below or above a tidal volume threshold, determine , as a second determination, whether an inhalation flow rate for a respective inhalation of the plurality of inhalations is below or above an inhalation flow rate threshold, and to generate , on a graphical , acoustical and / or haptical user interface of the device 20 , a guidance indication based on the first and second determination . In other words , using the first and second determination, the control unit continuously generates , for respective or each of the inhalations , a real-time breath-guidance indicating a user action to be taken when interacting with the inhalation device .

[0082] Here , the first determination may be a determination whether a tidal volume for a respective inhalation, as measured by a sensor at the inhalation device and communicated via the wireless communication connection, for example at an end of a single inhalation, has reached the tidal volume threshold or is above / below the tidal volume threshold of , for example , 700 ml . The guiding algorithm continuously, over the respective inhalations , guides the user to an inhalation action to inhale an amount of tidal volume that is above the tidal volume threshold, in other words to perform a deep inhalation . This user guidance to interact with the inhalation device reduces the influence of anatomy dead spaces and results in a user inhalation in which the generated aerosol can reach deeper into the lung .

[0083] Here , the second determination may be a determination whether an inhalation flow rate , as measured by a sensor at the inhalation device and communicated via the wireless communication connection, for example reached at an end or at a peak of a s ingle inhalation, for a respective inhalation of the plurality of inhalations is below or above the inhalation flow rate threshold of , for example , 30 L / min . The guiding algorithm continuously, over the respective inhalations , guides the user to an inhalation action to adhere to an inhalation speed or flow rate that is below the inhalation flow rate threshold, e . g . 30 L / min, in other words to perform a slow inhalation . This user guidance to interact with the inhalation device reduces aerosol losses in the throat , increases residence times to enhance sedimentation of the generated aerosol in the lungs . Advantageously, the combination of performing continuous guidance on both the tidal volume and the inhalation flow rate also causes , as synergetic effect , that the inhalation duration becomes longer than the corresponding exhalation duration ( increased duty cycle ) which overall reduces treatment times and reduces unwanted variability between individual inhalation performances . The skilled person understands that reduced variability corresponds to a more even breathing maneuver , which may also allow for a more accurate pre-off trigger and therefore higher lung deposition . Continuous guiding also supports higher therapy adherence and collection and transfer of data supports capability for an earlier intervention by physicians .

[0084] The continuous guidance is preferably generated using an acoustical and / or haptical ( tactible ) user interface 23 providing interaction with the user . This advantageously takes into account human physiology during the inhalation process in which the user becomes more rapidly susceptible to acoustical and / or haptical ( tactible ) guidance than simultaneously also visually monitoring a graphical user interface .

[0085] Preferably, the generated guidance indicates , at interface 23 , a corrective action to change the tidal volume ( to breath deeper ) and / or the inhalation flow rate ( to breath slower ) during the inhalation session, in particular during or after an inhalation or a number of initial inhalations . The generated guidance may also indicate a maintaining action to maintain the tidal volume ( to continue breathing in the same volume ) and / or the inhalation flow rate ( to maintain the inhalation or exhalation speed ) during the inhalation session, in particular after an inhalation or a number of initial inhalations .

[0086] Preferably, the control unit 22 may further be configured to dynamically adapt the tidal volume threshold and / or the inhalation flow rate threshold . That is , using measured tidal volume data and / or measured inhalation flow data during the inhalation session, for example for an initial set of inhalations and exhalation, such as after 3 inhalations , the control unit may determine that the user does not perform an inhalation process according to the prescribed thresholds , for example because of a temporary medical condition ( such as high blood pressure , temporary illness , fever or the like ) or because of a continuous status ( such as small persons with small lung volumes and therefore low tidal volumes ) , and therefore the control unit 22 dynamically adapts the thresholds either according to predefined change settings or in combination with the measured tidal volume data and / or measured inhalation flow data, to better guide the user according to the daily condition . According to another example of the adaptive setting, the control unit 22 may increase the tidal volume threshold by a predetermined percentage or amount , if at least a certain number of inhalations in a row, such as 3 inhalations , exceed the present tidal volume threshold . If that threshold is not exceeded, on the other hand, the present tidal volume threshold is maintained .

[0087] The dynamic adaptation may be performed after the initial set of inhalations and exhalation to adapt the continued guidance during the remainder of the inhalation session . When dynamically adapting the thresholds , the control unit 22 may also increase or decrease the number of inhalations in the inhalation session, and provide corresponding guidance , so that a prescribed amount of medication according to a therapy plan is administered . The dynamic adaptation during the continuous guiding may continuously adapt the thresholds to the patients breathing capacity if necessary .

[0088] For example , the control unit 22 may be configured to set an increased tidal volume threshold if a plurality of subsequent inhalations exceed the tidal volume threshold . Furthermore , the control unit 22 may further be configured to set a decreased tidal volume threshold if a plurality of subsequent inhalations do not exceed the tidal volume threshold or do not reach a specific percentage of the tidal volume threshold . For example , the tidal volume threshold may be reduced only when the control unit determines that a specific number of inhalations ( e . g . three successive inhalations ) remain at or below 80% of the tidal volume threshold . The control unit 22 may further be configured in such a way that the tidal volume threshold is settable ( only) between a minimum value and a maximum value . This takes into account that user variability should be adapted and guided within a lower and an upper bound .

[0089] Preferably, the control unit 22 may further be configured to determine whether respective inhalation flow rates and / or tidal volumes decrease or increase over time for a plurality of inhalations . In other words , the above first and second determinations may be evaluated for a sequence of inhalations so that an early detection of a behavioral inhalation change over a time period longer than a single inhalation can be considered for improved guidance .

[0090] Accordingly, control unit 22 may also determine a trend in the tidal volumes and / or inhalation flow rates over a plurality of inhalations or also over a plurality of inhalation sessions , and to generate the guidance indication using the determined trend . In other words , even if the prescribed thresholds ( for a slow and deep inhalation ) are met , the control unit may determine an upwards or downwards trend and can therefore generate a prediction ( for example , using linear or non-linear regression methods ) that the prescribed thresholds may not be reached in a number of inhalations . This provides an early indication and can thus be used as a guidance indication for an earlier correction of the inhalation interaction of the user with the inhalation device . The skilled person understands that this can lead to a further reduction in the variance of the inhalation process .

[0091] Preferably, the control unit 22 may further be configured to exclude a ( first ) inhalation ( i . e . one of the inhalations during the inhalation session) of the user during the inhalation session from the continued breath guidance and / or dynamic adaptation of the respective thresholds ( tidal volume threshold and / or tidal volume threshold) if a corresponding ( first ) inhalation duration is shorter than a predefined duration . This advantageously takes into account that the user / patient may have the urge to clear the throat or for a short-time coughing . While this may interrupt the inhalation process , and thus may lead to measured tidal volumes and / or inhalation flow rates that are far from expected values ( according to the thresholds ) , such short time interruptions and the corresponding measured tidal volumes and / or inhalation flow rates should be disregarded for the continuous guiding feedback, as this would otherwise significantly disrupt the guiding process ( and the associated statistics and trend analysis ) .

[0092] Preferably, the control unit 22 may further be configured to , during the inhalation session, continuously determine , as a third determination, whether an inhalation duration for a respective inhalation of the plurality of inhalations is longer or shorter as a corresponding exhalation of the plurality of exhalations or reaches a prescribed duration threshold . The user interface of the control device may then further generate a guidance indication based on the first determination, the second determination and the third determination .

[0093] The device 20 may further comprise an acoustic detection unit , such as a microphone . The acoustic detection unit may be adapted to acquire acoustic measurement data of the user when using the aerosol nebulizer system . Advantageously, the control unit 22 may control the acoustic detection unit to acquire acoustic measurement data during the inhalation session, and to stop acquiring acoustic measurement data before or after the inhalation session . Using the acoustic measurement data , the control unit may further be configured to perform a cough monitoring , e . g . to determine a coughing frequency or coughing duration, and may also exclude ( data related to ) a ( second) inhalation ( i . e . one of the inhalations during the inhalation session) of the user during the inhalation session from the continued breath guidance if the acquire acoustic data indicate a coughing of the user . Here , the control unit 22 may determine a number of coughing events or a coughing frequency and may thus determine that the user has interrupted the inhaling the aerosol . After such an interruption process due to monitored coughing , the control unit 22 may preferably reset the above threshold to initial values , in particular to again guide the user to a preferred inhalation process over a plurality of inhalations .

[0094] Preferably, the control unit 22 may further be configured to determine whether a complete amount of medication has been used for generating the aerosol , in other words , whether the liquid medication has been consumed . The control unit 22 may determine a usage state of the liquid medication us ing measured date indicating a fill state at the aerosol generator or a liquid presence state at the aerosol generator . The continued guidance may then appropriately indicate that an appropriate end of the inhalation session has been reached . The end of the inhalation session may also cause the control unit 22 to provide a final report of the inhalation session .

[0095] Preferably, the control unit 22 may further be configured to determine whether a minimum aerosol generation time has been reached . The control unit 22 may determine such a minimum aerosol generation time using usage data transmitted from the aerosol nebulizer indicating a starting time or respective starting times after a breath trigger causes the aerosol generator to start generating aerosol .

[0096] According to a further embodiment , a computer program comprising instructions to cause the control device 20 as described above to execute the steps of : establishing a wireless communication connection and performing data transmission with the aerosol nebulizer system 30 , the data transmission including inhalation data of a plurality of inhalations and exhalations of a user during the inhalation session; and during the inhalation session, continuously : determining , as a first determination, whether a tidal volume for a respective inhalation of the plurality of inhalations is below or above a tidal volume threshold determining, as a second determination, whether an inhalation flow rate for a respective inhalation of the plurality of inhalations is below or above a inhalation flow rate threshold, and generating a guidance indication based on the first and second determination . In other words , the computer program may be a pre -installed or downloadable ( e . g . from a server ) program, which may also be referred to as an APP . When storing the APP on a mobile device or computing device , the mobile device operates as the device 20 for providing continued breath guidance when using an aerosol nebulizer system 30 during an inhalation session .

[0097] The computer or application program may be stored in a memory unit 25 , of the control device 20 and may be started from there within the framework of the operating system of the control device 20 . Furthermore , it is alternatively possible to transfer an application program into the memory unit 25 of the control device 20 via an interface , for example the communication unit 21 or an additional interface ( RS-232 , USB, FireWire , or the like ) and to start it from there within the framework of the operating system of the control device 20 . Finally, such an application program may be loaded into the memory unit 25 of the control device 20 via a remote data connection unit ( not shown ) , for example downloaded via the Internet , and may be started from there within the framework of the operating system of the control device 20 .

[0098] EXAMPLES

[0099] In a preferred example of the present disclosure and invention, the inhalation device is a compact handheld medical device in which the signalling unit is integrated in the form of multi-colour light sources , preferably one or more LEDs and a vibrator . The ongoing inhalation process of the user / patient is monitored by the sensing unit and its related hardware components and the data obtained processed by the control unit . If , for example , the present breath flow rate momentarily exceeds the first pre-set threshold value of 30 1 / min or preferably 40 1 / min, the control unit triggers the signalling unit to output a first short vibration signal . This signal will be felt by the user / patient , making him or her aware that the ongoing inhalation process is non-optimal . If the user / patient continues the inhalation process and further increase the breath flow rate , for example , beyond the second pre-set threshold value of 75 1 / min, the control unit triggers the signalling unit to output the second signal in the form of a stronger or longer vibration signal in combination with an alerting light signal from a transparent top region of the inhalation device , for example , a yellow or red light signal . The user / patient is thus alerted that the quality of the ongoing inhalation process has worsened . Optionally, the first vibration signal may already be accompanied by a yellow or red light signal to avoid that the user / patient misunderstands the first vibration signal to be of positive nature . Also , the first and second signal may simply be indicative of how the user / patient exceeds an optimal breath flow rate . If and whenever the user / patient exceeds the first threshold of 30 or 40 1 / min, the first signal is output . If and whenever the degree of deviation is larger , for example , a breath flow rate of 75 1 / min or more , the second signal is output . Further optionally, the threshold values are adaptable , for example , to the default breathing and inhalation of individual users / patients or to the default breathing and inhalation of the current inhalation session based on the individual daily characteristics and wellbeing of the patient / user and the course of the inhalation process .

[0100] By means of the respective alarms given, the user / patient obtains a chance to improve the inhalation process by adapting his or her inhalation actions . The exemplified first signal and second signal herein basically represent a signal cascade or an alarm cascade to make the user / patient aware of deficits in the ongoing inhalation process . The fourth signal being indicative of the inhalation device involved being inoperable can in the present example be output by a red light signal emanating from the housing of the inhalation device . As another parameter, the tidal volume can be considered and a significant pre-set threshold value is 1 . If said value is underrun, the user / patient is alerted and instructed to take deeper breath through the inhalation device .

[0101] A yet further non-limiting example of the present disclosure and invention is either separate or combinable with the above example and relates to the option of having the signalling unit external and integrated into an external electronic device consisting of or comprising an electronic display device . In this scenario , once again, an ongoing inhalation process is monitored by the sensing unit , the data obtained and processed by the control unit and the signalling unit is controlled by the control unit to output respective signals . In the present example , an external signalling unit can have an output similar as described above , where the external electronic device outputs a first signal representative of a first alarm and a second signal representative of a second alarm . It is within the nature of the electronic device or the electronic display device that the respective signals can come in many different forms and do not necessarily need to be limited to a combination of vibration and light signals . Instead, it is conceivable that the respective alarms are output by suitable graphical , written and / or voice information . The respective alarms could be output also in addition to any type of alarm output directly on the inhalation device . In the present example , the external signalling unit can also output the third signal in any conceivable form to illustrate relevant parameters of the ongoing inhalation process . As a specific example , the external signalling unit can display a schematic lung illustration that in turn via animations can illustrate the depth and quality of the inhalation live and continuously as the inhalation process progresses . In the present example , the external signalling unit is configured to and outputs inhalation process / breath guiding information to the user / patient that contain recommendations and instructions on how to improve and ongoing inhalation process also with respect to any possible alarm previously output .

[0102] A fluid or liquid to be nebulised or aerosolised by the aerosol generator may be a fluid or liquid for the generation of a pharmaceutical aerosol for the delivery of an active compound .

[0103] An active compound is a natural , biotechnology-derived or synthetic compound or mixture of compounds useful for the diagnosis , prevention, management or treatment of a disease , condition or symptom of a mammal , in particular a human . Other terms which may be used as synonyms of active compounds include , for example , active ingredient, active pharmaceutical ingredient, drug substance, diagnostic material, drug, medicament and the like. The fluid could be of a liquid, solution, suspension, colloidal mixture or liposomal formulation form and can be prepared, mixed or opened before or during the application.

[0104] The active compound comprised in the fluid to be nebulised or aerosolised by the aerosol generator may be a drug substance or a medicament which is useful for the prevention, management, diagnosis or treatment of any disease, symptom or condition affecting the body, skin, body cavities, the abdomen, the eyes, the ear, the intestine, the stomach, the nose, the nasal cavities, the sinuses, the osteomeatal complex, the mouth, the trachea, the lungs, upper lungs, lower lungs, central lungs, the bronchia, the bronchioles, the alveoli and / or the respiratory tract. In particular an aerosol comprising an active compound, which is useful for the prevention, management, diagnosis or treatment of any pulmonary or respiratory disease, symptom or condition. The active compound comprised in the fluid to be nebulised or aerosolised by the aerosol generator may be used especially for clinical trials or regulatory approvals.

[0105] Among the active compounds which may be useful for serving one of the purposes named previously and that may be used together with the present invention, are, for example, substances selected from the group consisting of anti-inflammatory compounds, anti-infective agents, antiseptics, prostaglandins, endothelin receptor agonists, phosphodiesterase inhibitors, beta-2-sympathicomimetics , decongestants, vasoconstrictors, anticholinergics, immunomodulators, immunoglobulins, mucolytics, anti-allergic drugs, antihistaminics , mast-cell stabilising agents, tumor growth inhibitory agents, wound healing agents, local anaesthetics, antioxidants, oligonucleotides, peptides, proteins, vaccines, vitamins, plant extracts, cholinesterase inhibitors, vasoactive intestinal peptide, serotonin receptor antagonists, and heparins, glucocorticoids, anti-allergic drugs, antioxidants, vitamins, leucotriene antagonists, anti-infective agents, antibiotics, antifungals, antivirals, mucolytics, decongestants, antiseptics, cytostatics, immunomodulators , vaccines, wound healing agents, local anaesthetics, oligonucleotides, xanthin derived agents, peptides, proteins and plant extracts . Such compound may be used in the form of a suspension, a solution, a colloidal formulation (i.e. , liposomal) , etc.

[0106] Examples of potentially useful anti-inflammatory compounds are glucocorticoids and non-steroidal anti-inflammatory agents such as arf ormoterole, betamethasone, beclomethasone, budesonide, ciclesonide, dexamethasone, desoxymethasone, fluoconolone acetonide, f luocinonide, flunisolide, fluticasone (propionate) , formoterole, fumarate, icomethasone , rofleponide, tiotropium, triamcinolone acetonide, fluocortin butyl, hydrocortisone, hydroxycort isone-17 -butyrate, pr edni carbat e , 6 -methylprednisolone aceponate, mometasone furoate, pirfenidone, dehydroepiandrosteronesulfate (DHEAS) , tartrate, umeclidinium, vilanterol, elastane, prostaglandin, leukotriene, bradykinin antagonists, non-steroidal anti-inflammatory drugs (NSAIDs) , such as ibuprofen and acetylsalicylic acid (ASA) , including any pharmaceutically acceptable salts, esters, isomers, stereoisomers, diastereomers, epimers, solvates or other hydrates, prodrugs, derivatives, or any other chemical or physical forms of active compounds comprising the respective active moieties and combination thereof, like for example LABA and LAMA combination like aclidinium and formoterol.

[0107] Examples of anti-infective agents, whose class or therapeutic category is herein understood as comprising compounds which are effective against bacterial, fungal, and viral infections, i.e. encompassing the classes of antimicrobials such as for example bacteriophages (for example the treatment of pulmonary infections in cystic fibrosis patients) or antimicrobial petides (for example for the treatment of MDR G negative Pneumonia) , antibiotics, antifungals, antiseptics, and antivirals, are penicillins, including benzylpenicillins (penicillin-G- sodium, elemizone penicillin, benzathine penicillin G) , phenoxypenicillins (penicillin V, propicillin) , aminobenzylpenicillins (ampicillin, amoxycillin, bacampicillin) , acylaminopenicillins (azlocillin, mezlocillin, piperacillin, apalcillin) , carboxypenicillins ( carbenicillin, ticarcillin, temocillin) , isoxazolyl penicillins (oxacillin, cioxacillin, dicloxacillin, flucioxacillin) , and amiidine penicillins (mecillinam) ; cephalosporins, including cefazolins (cefazolin, cefazedone) ; cefuroximes (cefuroxim, cefamandole, cefotiam) , cefoxitins (cefoxitin, cefotetan, latamoxef, flomoxef ) , cefotaximes (cefotaxime, ceftriaxone, ceftizoxime, cefmenoxime) , ceftazidimes (ceftazidime, cefpirome, cefepime) , cefalexins (cefalexin, cefaclor, cefadroxil, cefradine, loracarbef , cefprozil) , and cefiximes (cefixime, cefpodoxim proxetile, cefuroxime axetil, cefetamet pivoxil, cefotiam hexetil) , loracarbef, cefepim, clavulanic acid / amoxicillin, Cef tobiprole; synergists, including beta-lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam; carbapenems, including imipenem, cilastin, meropenem, doripenem, tebipenem, ertapenem, ritipenam, and biapenem; monobactams, including aztreonam; aminoglycosides, such as apramycin, gentamicin, amikacin, isepamicin, arbekacin, tobramycin, netilmicin, spectinomycin, streptomycin, capreomycin, neomycin, paromoycin, and kanamycin; macrolides, including erythromycin, clarythromycin, roxithromycin, azithromycin, dithromycin, josamycin, spiramycin and telithromycin; gyrase inhibitors or f luroquinolones , including ciprofloxacin, gatif loxacin, norfloxacin, ofloxacin, levofloxacin, perfloxacin, lomef loxacin, fleroxacin, garenoxacin, clinaf loxacin, sitaf loxacin, prulif loxacin, olamuf loxacin, caderof loxacin, gemif loxacin, balof loxacin, trovaf loxacin, and moxif loxacin; tetracyclins , including tetracyclin, oxytetracyclin, rolitetracyclin, minocyclin, doxycycline, tigecycline and ami no eye line; glycopeptides, inlcuding vancomycin, teicoplanin, ristocetin, avoparcin, oritavancin, ramoplanin, and peptide 4; polypeptides, including plectasin, dalbavancin, daptomycin, oritavancin, ramoplanin, dalbavancin, telavancin, bacitracin, tyrothricin, neomycin, kanamycin, mupirocin, paromomycin, polymyxin B and colistin; sulfonamides, including sulfadiazine, sulfamethoxazole, sulfalene, co-trimoxazole , co-trimetrol, co-trimoxazine, and co- tetraxazine ; azoles, including clotrimazole, oxiconazole, miconazole, ketoconazole, itraconazole, fluconazole, metronidazole, tinidazole, bifonazol, ravuconazol, posaconazol, voriconazole, and ornidazole and other antifungals, antimycotics , fungicide or fungistatic, such as for example flucytosin, griseofulvin, tolnaftal, naftifin, terbinafin, amorolfin, ciclopiroxolamin, echinocandins, such as micafungin, caspofungin, anidulafungin, amphotericin B or variconazole; nitrofurans, including nitrofurantoin and nitrofuranzone; polyenes, including amphotericin B, natamycin, nystatin, flucytosine ; other antibiotics, including tithromycin, lincomycin, clindamycin, oxazolindiones ( linzezolids ) , ranbezolid, streptogramine A+B, pristinamycin A+B, Virginiamycin A+B, dalfopristin / quinupristin (Synercid) , chloramphenicol, ethambutol, pyrazinamid, terizidon, dapson, prothionamid, fosfomycin, fucidinic acid, rifampicin, isoniazid, cycloserine, terizidone, ansamycin, lysostaphin, iclaprim, mirocin B17, clerocidin, filgrastim, formycin, pentamidine, and Fab-I-Inhibitors ;

[0108] Usful drugs may be afabicine and / or derivates thereof; antivirals, including aciclovir, ganciclovir, birivudin, valaciclovir , zidovudine, didanosin, thiacytidin, stavudin, lamivudin, zalcitabin, ribavirin, nevirapirin, delaviridin, trifluridin, ritonavir, saquinavir, indinavir, foscarnet, amantadin, podophyllotoxin, vidarabine, tromantadine, and proteinase inhibitors, siRNA based drugs; antiseptics, including acridine derivatives, iodine-povidone, benzoates, rivanol, chlorhexidine , quarternary ammonium compounds, cetrimides, biphenylol, clorofene, and octenidine; plant extracts or active ingredients of plants, such as plant extracts from chamomile, hamamelis, echinacea, calendula, thymian, papain, pelargonium, pine trees, essential oils, myrtol, pinen, limonen, cineole, thymol, mentol, camphor, tannin, alpha-hederin, bisabolol, lycopodin, vitapherole; useful drugs may be plant extracts of cannabinoids, active ingredients of cannabinoids, such as for example terahydrocannabinol, and / or derivates of active inredients of cannabinoids; wound healing compounds, including pirfenidone, dexpantenol, allantoin, vitamins, hyaluronic acid, alpha-antitrypsin, anorganic and organic zinc salts / compounds , salts of bismuth and selen;

[0109] - Useful drugs may be syntetic analogues of prostacyclines and / or derivates thereof; useful drugs may be gluthathione and / or derivates thereof;- antifibrotic compounds, for example, pirfenidone; interferones (alpha, beta, gamma) , tumor necrosis factors, cytokines, interleukines ; immunomodulators, including immunosuppressive compounds, antibody (Ab) , cytostatics and metastasis inhibitors; - immunosuppressive compounds, including glucocorticoids, cytostatics, , drugs acting on immunophilins or on other drugs, such as interferons, opioids, TNF binding proteins or mycophenolate; immunosuppressive compounds, including immunomodulating agents, or immunosuppressive agents or antirejection medications are compounds that may for example inhibit or prevent activity of the immune system, for example to prevent graft rejection; immunosuppressive compounds, including drugs acting on immunophilins, such as ciclosporin, tacrolimus, sirolimus, everolimus, mycophenolic acid, also called mycophenolate or mycophenolate-mofetil, methotrexat, or azathioprine; antibody (Ab) , including polyclonal antibodies or monoclonal antibodies, such as for for example immunoglobulin (Ig) , immunoglobulin G (IgG - for example Privigen - IgProlO) , immunoglobulin A (IgA) , or immunoglobulin M (IgM) ; as well as fragments of antibodies, also known as Fab (fragment, antigenbinding) region, complementarity determining regions (CDRs) , Fc (Fragment, crystallizable) region, or Fc receptors; or nanobodies for example for the treatment of RSV; cytostatics and metastasis inhibitors, including chemotherapeutic agents or anti-cancer drugs, such as alkylating agents, antimetabolite, antimicrotubuli agents, anthracyclines , cisplatin, cyclophosphamid, cytoskeletal disruptors (taxanes) , epothilones, histone deacetylase inhibitors, ifosfamid, inhibitors of topoisomerase I + II, intercalating agents, kinase inhibitors, mitomycin, nucleotide analogs and precursor analogs, peptide antibiotics, nanododies, platinum-based agents, retinoids, and vinca alkaloids and derivatives; alkylating agents, such as nimustine, melphanlane, carmustine, lomustine, cyclophosphosphamide, mechlorethamine , dacarbazine, nitrosoureas, temozolomide (oral dacarbazine) , ifosfamide, trofosfamide, chlorambucil, busulfane, treosulfane, prednimustine , thiotepa; antimetabolites, e.g. cytarabine, fluorouracil, methotrexate, mercaptopurine, tioguanine; taxane, such as paclitaxel, abraxane, taxotere or docetaxel; topoisomerase I inhibitors, such as topotecan or irinotecan; topoisomerase II inhibitors, such as doxorubicin or etoposid; intercelating agents, such as anthracyclines , like doxorubicin; platinum-based agents, such as cisplatin, carboplatin, oxaliplatin, or satraplatin; alkaloids, such as vinblastine, vincristine, vindesine; antibiotics, such as alcarubicine , bleomycine, dactinomycine , daunorubicine, doxorubicine , epirubicine, idarubicine, mitomycine, plicamycine ; complexes of transition group elements (e.g. Ti, Zr, V, Nb, Ta, Mo, W, Pt) such as carboplatinum, cis-platinum and metallocene compounds such as titanocendichloride; amsacrine, dacarbazine, estramustine, etoposide, beraprost, hydroxycarbamide, mitoxanthrone , procarbazine, temiposide; paclitaxel, docetaxel, gefitinib, vandetanib, erlotinib, poly- ADP-ribose-polymerase (PRAP) enzyme inhibitors, banoxantrone, gemcitabine, pemetrexed, bevacizumab, ranibizumab. Examples of potentially useful mucolytics are DNase, P2Y2-agonists (denufosol) , drugs affecting chloride and sodium permeation, such as sodium chloride (NaCl, e.g. , 0.9%, 3%, 6%, 7% solutions) , ectoine (1,4,5, 6-tetrahydro-2-methyl-4 -pyrimidine carboxylic acid) , N- ( 3 , 5- Diamino-6-chloropyrazine-2-carbony) -N'-{4-[4-(2,3- dihydroxypropoxy ) -phenyl ] butyl } guanidine methanesulfonate ( PARION 552-02) , heparinoids, guaifenesin, acetylcysteine, carbocysteine, ambroxol, bromhexine, tyloxapol, lecithins, myrtol, surfactant, synthetic surfactant and recombinant surfactant proteins.

[0110] Example for a pulmonary surfactant (derived from: surface active agent) , which support pulmonary development, may be, an exogenous pulmonary surfactant, or belong to the class of "modified natural" pulmonary surfactants, which are lipid extracts of minced mammalian lung or lung lavage. These preparations have variable amounts of SP-B and SP-C proteins and, depending on the method of extraction, may contain non-pulmonary surfactant lipids, proteins or other components. Some of the modified natural pulmonary surfactants present on the market, like SurvantaTM, are spiked with synthetic components such as tripalmitin, dipalmitoylphosphatidylcholine and palmitic acid.

[0111] Example of current modified natural pulmonary surfactants include, but are not limited to, bovine lipid pulmonary surfactant (BLESTM, BLES Biochemicals, Inc. London, Ont) , calfactant (InfasurfTM, Forest Pharmaceuticals, St. Louis, Mo. ) , bovactant ( Alveof actTM, Thomae, Germany) , bovine pulmonary surfactant (Pulmonary surfactant TATM, Tokyo Tanabe, Japan) , and beractant (SurvantaTM, Abbott Laboratories, Inc., Abbott Park, Ill. ) .

[0112] Example of pulmonary surfactant, which may belong to the class of "artificial" pulmonary surfactants, are simply mixtures of synthetic compounds, primarily phospholipids and other lipids that are formulated to mimic the lipid composition and behaviour of natural pulmonary surfactant and are devoid of pulmonary surfactant proteins, are artificial surfactants include, but are not limited to, pumactant (AlecTM, Britannia Pharmaceuticals, UK) , and colfosceril palmitate ( Exosurf TM, GlaxoSmithKline, pic, Middlesex) .

[0113] Example of pulmonary surfactant, which may belong to the class of "reconstituted" pulmonary surfactants, are artificial pulmonary surfactants to which have been added pulmonary surfactant proteins / peptides isolated from animals or proteins / peptides manufactured through recombinant technology such as those described in WO 95 / 32992, or synthetic pulmonary surfactant protein analogues such as those described in WO 89 / 06657, WO 92 / 22315 and WO 00 / 47623, are reconstituted surfactants include, but are not limited to, poractant alfa (CurosurfTM Chiesi Farmaceutici S.p.A. ) and lucinactant (SurfaxinTM, Windtree Therapeutics, Inc., Warrington, Pa. ) and the product having the composition disclosed in WO 2010 / 139442.

[0114] Examples of potentially useful vasoconstrictors and decongestants which may be useful to reduce the swelling of the mucosa are phenylephrine, naphazoline, tramazoline, tetryzoline, oxymetazoline, f enoxazoline , xylometazoline, epinephrine, isoprenaline, hexoprenaline , and ephedrine.

[0115] Examples of potentially useful local anaesthetic agents include benzocaine, tetracaine, procaine, lidocaine and bupivacaine .

[0116] Examples of potentially useful antiallergic agents or antiasthma compounds include the afore-mentioned glucocorticoids, cromolyn sodium, nedocromil, cetrizin, loratidin, montelukast, roflumilast, ziluton, omalizumab, heparinoids and other antihistamins , including azelastine, cetirizin, desloratadin, ebastin, fexofenadin, levocetirizin, loratadin.

[0117] Examples of potentially useful anticholinergic agents include ipratropium bromide, tiotropium bromide, oxitropium bromide, glycopyrrolate . Examples of potentially useful beta-2-sympathicomimetic agents include salbutamol, fenoterol, formoterol, indacaterol, isoproterenol, metaproterenol , salmeterol, terbutaline, clenbuterol, isoetarine, pirbuterol, procaterol, ritodrine and long- acting beta-agonists (LABAs) such as Albuterol sulphate, formoterol fumarate, salmeterol xinafoate, arformoterol tartrate, and olodaterol.

[0118] Examples of potentially useful muscarinic antagonists are muscarine and nicotine, such as ipratropium bromide and acetylcholine as well as long-acting muscarinic antagonists (LAMA) such as aclidinium (bromide) , glycopyrronium (bromide) , ipratropium, tiotropium (bromide) , and umeclidinium (bromide) .

[0119] Examples of xanthine derived agents include theophylline, theobromine, caffeine.

[0120] Example of PDE5-Inhibitor include sildenafil.

[0121] Example of antisense oligonucleotides are short synthetic strands of DNA (or analogs) that are complimentary or antisense to a target sequence (DNA, RNA) designed to halt a biological event, such as transcription, translation or splicing. The resulting inhibition of gene expression makes oligonucleotides dependent on their composition useful for the treatment of many diseases and various compounds are currently clinically evaluated, such as ALN- RSV01 to treat the respiratory syncytical virus by, AVE-7279 to treat asthma and allergies, TPI-ASM8 to treat allergic asthma, 1018- ISS to treat cancer. Examples of potentially useful peptides and proteins include antibodies against toxins produced by microorganisms, antimicrobial peptides (for example for the treatment of MDR G negative Pneumonia) , such as cecropins, defensins, thionins, and cathelicidins.

[0122] Example of radioactive agents for diagnoses or clinical trials, such as technetium 99m [Tc99, Technegas, Technetium (99mTc) , Technetium-99 (99Tc) ] , krypton (81mKr) inhalation gas, and Xenon- 133 [Xenon Xe-133] . A number of isotopes, such as iodine-131 (1311) , phosphorous-32 (32P) , strontium-90 (90Sr) , and yttrium-90 (90Y) , may be used. Especially for a pulmonary ventilation and blood perfusion (V / Q) diagnose scan or scintigraphic pulmonary deposition studies the isotopes, krypton (81mKr) inhalation gas or technetium 99m (99mTc) , may be used.

[0123] Example of potentially useful opioids, such as endogenous opioids, opium alkaloids and derivatives, synthetic opioids, allosteric modulators, and opioid antagonists.

[0124] Useful drugs may be biosililars such as for example Dornase- Alpha for cystic fibrosis patients;

[0125] The nebulizer may be used with fluids or liquids of the groups of viral gene therapy agents or non-viral gene therapy agents . The transferred nucleotide constructs may be single or double stranded DNA, RNA, or siRNA. In one study the gene therapeutic agent carries especially the CF gene to substitute and cure the cystic fibrosis deficiency. For the transfer to the patient the substitute is integrated in a viral vector and masked in liposomes. The, from UK CF Gene Therapy Consortium (GTC) called, inhalative gene therapeutic agent "pGMl 69 / GL67A" is under clinical evaluation.

Claims

CLAIMS1. A device (20) for providing continued breath guidance when using an aerosol nebulizer system (30) during an inhalation session, said aerosol nebulizer system (30) comprising an aerosol generator (31) for nebulizing a liquid or an aerosol source for dispensing aerosol, the device (20) comprising: a communication unit (21) , configured to establish a wireless communication connection and to perform data transmission with the aerosol nebulizer system (30) , the data transmission including inhalation data of a plurality of inhalations and exhalations of a user during the inhalation session; a control unit (22) , configured to, during the inhalation session, continuously: determine, as a first determination, whether a tidal volume for a respective inhalation of the plurality of inhalations is below or above a tidal volume threshold, determine, as a second determination, whether an inhalation flow rate for a respective inhalation of the plurality of inhalations is below or above an inhalation flow rate threshold, generate, on a graphical user interface of the device, a guidance indication based on the first and second determination .

2. The device (20) of claim 1, wherein the generated guidance indication indicates a corrective action to change the tidal volume and / or the inhalation flow rate during the inhalation session .

3. The device (20) of one of claims 1 - 2, wherein the control unit (22) is further configured to dynamically adapt the tidal volume threshold and / or the inhalation flow rate threshold.

4. The device (20) of claim 3, wherein the control unit (22) is further configured to set an increased tidal volume threshold if a plurality of subsequent inhalations exceed the tidal volume threshold.

5. The device (20) of one of claims 1 - 4, wherein the control unit (22) is further configured to set a decreased tidal volume threshold if a plurality of subsequent inhalations do not exceed the tidal volume threshold.

6. The device (20) of any of claims 1 - 5, wherein the tidal volume threshold is settable between a minimum value and a maximum value.

7. The device (20) of one of claims 1 - 6, wherein the control unit (22) is further configured to determine whether respective inhalation flow rates and / or tidal volumes for the plurality of inhalations decrease or increase over time.

8. The device (20) of one of claims 1 - 7, wherein the control unit (22) is further configured to determine a trend in the tidal volumes and / or inhalation flow rates, and to generate the guidance indication using the determined trend.

9. The device (20) of one of claims 1 - 8, wherein the control unit (22) is further configured to exclude an inhalation of the user during the inhalation session from the continued breath guidance and / or dynamic adaptation of thresholds if a corresponding inhalation duration is shorter than a predefined duration .

10. The device (20) of one of claims 1 - 9, wherein the control unit (22) is further configured to, during the inhalation session, continuously: determine, as a third determination, whether an inhalation duration for a respective inhalation of theplurality of inhalations is longer or shorter as a corresponding exhalation of the plurality of exhalations , generate , on the graphical user interface of the device , a guidance indication based on the first determination, the second determination and the third determination .11 . The device ( 20 ) of one of claims 1 - 10 , wherein the device further comprises an acoustic detection unit , the acoustic detection unit to acquire acoustic data of the user when using the aerosol nebulizer system, wherein the control unit is further configured to exclude an inhalation of the user during the inhalation session from the continued breath guidance if the acquired acoustic data indicate a coughing of the user .12 . A computer program comprising instructions to cause the control device ( 20 ) of any of claims 1 - 11 to execute the steps of : establishing a wireless communication connection and performing data transmission with the aerosol nebulizer system ( 30 ) , the data transmission including inhalation data of a plurality of inhalations and exhalations of a user during the inhalation session; and during the inhalation session, continuously : determining , as a first determination, whether a tidal volume for a respective inhalation of the plurality of inhalations is below or above a tidal volume threshold, determining , as a second determination , whether an inhalation flow rate for a respective inhalation of the plurality of inhalations is below or above an inhalation f low rate threshold, generating a guidance indication based on the first and second determination .13 . A method of operating an inhalation device that includes :a sensing unit configured to monitor an inhalation process , to measure inhalation process parameters and to collect data of and during the inhalation process , and a control unit configured to receive and process the data collected by the sensing unit and to generate a control signal for a signalling device , wherein the method comprises : monitoring an inhalation process comprising measuring inhalation process parameters and collecting data of and during the inhalation process , generating and sending a control signal based on the collected data to a signalling unit configured to output a signal , preferably an optical , acoustic and / or a tactile s ignal , wherein in response to said control signal , the signalling unit outputs : a first signal if and whenever a first pre-set threshold value of an inhalation process parameter is underrun or exceeded during the inhalation process and a second signal if and whenever a second pre-set threshold value of an inhalation process parameter, that is different from the first pre-set threshold value , is underrun or exceeded during the inhalation process , and / or a third signal that is indicative of one or more inhalation process parameters and continuously output during part or all of the inhalation process .14 . The method according to claim 13 , wherein the first signal is a first vibration signal and / or a first light signal and the second signal is a combination of a second vibration signal that is stronger or different to the first vibration signal and / or a second light signal that is different to the first light signal .15 . The method according to claim 13 or 14 , further comprising generating and sending a control signal to the signalling unit , wherein in response to said control signal , the signalling unit outputs a fourth signal if and whenever the inhalation device is not ready for use .16 . The method according to any one of the claims 13 - 15 , wherein the signalling unit outputs the first signal if and whenever the first pre-set threshold value of an inhalation process parameter is exceeded or underrun during the inhalation process and outputs the second signal if and whenever the second pre-set threshold value of an inhalation process parameter, that is higher or lower than the first pre-set threshold value , is exceeded or underrun during the inhalation process .17 . The method according to claim 16 , wherein the inhalation process parameter is the breath flow rate and / or the tidal volume , and optionally wherein the first pre-set threshold of the breath flow rate is in the range of 30 1 / min or more , preferably 40 1 / min or more to less than 75 1 / min and the second pre-set threshold of the breath flow rate is 75 1 / min or more .18 . The method according to any one of claims 13 - 17 , wherein the signalling unit comprises or consists of any one of the following : means to generate an optical signal ; preferably a light signal and / or a written text , means to produce an acoustic signal ; preferably a sound and / or a voice signal , means to produce a tactile signal ; preferably a vibration signal and an electronic display device .19 . The method according to any one of claims 13 to 18 , wherein the signalling unit is implemented in the inhalation device itself .20 . The method according to claim 19 , wherein the first signal is a first vibration signal of the inhalation device and / or a first light signal from the inhalation device and the second signal is a combination of a second vibration signal of the inhalation device that is stronger or different to the first vibration and a second light signal from the inhalation device that is different to the first light signal , optionally whereinthe first and the second light signals are output from a top part of the inhalation device , which is made of translucent material through which the light signals are emitted .21 . The method according to claim 19 or 20 , wherein the fourth signal is a combination of a third vibration signal of the inhalation device and a sound signal from the inhalation device .22 . The method according to any one of claims 13 to 18 , wherein the signalling unit is implemented in a device different from and external to the inhalation device , preferably in an electronic device further preferably with a computer program stored on the electronic device configured to generate a graphical user interface for outputting data of the inhalation process .23 . The method according to claim 22 , wherein the signalling unit is an electronic display device and the method further comprises : in response to said control signal and during the inhalation process , the electronic display device outputs , preferably as the third signal , graphically and / or numerically and / or in writing and / or in written and spoken text at least one of the group of information consisting of : breath pattern, breath flow rate , peak flow rate , regularity of breathing cycles duration, tidal volume , inhaled volume , inhalation / exhalation ratio , respiratory minute volume , breathing frequency, breathing durations , breath pauses , live inhalation feedback information and instructions on how to optimize the ongoing inhalation process , wherein the displayed information is to inform a user of the inhalation device about the quality of the inhalation process and to trigger improvements of the inhalation process , and optionally the displaying of information is adj usted or stopped or suspended if and whenever a user of the inhalation device cannot abide to improve the inhalation process , and further optionallythe displaying of information is sorted according to the most important to the least important inhalation process parameters to be changed or improved .24 . The method according to any one of claims 13 - 23 , wherein the first signal and the second signal inform the user of the inhalation device about a non-optimal inhalation process and to trigger improvements of the inhalation process , and / or the first signal and the second signal are stopped or adj usted if a user of the inhalation device cannot abide to improve the inhalation process .25 . An inhalation device , optionally the one to carry out the method according to any one of claims 13 to 24 , comprising : a sensing unit configured to monitor an inhalation process and to measure and collect data of and during the inhalation process , a signalling unit configured to output a s ignal , preferably an optical , acoustic and / or a tactile signal , a control unit configured to receive and process the data collected by the sensing unit and to control the signalling unit based on said data , wherein the control unit is further configured to control the signalling unit such that the signalling unit outputs a first signal if and whenever a first pre-set threshold value of an inhalation process parameter is underrun or exceeded during the inhalation process and outputs a second signal if and whenever a second pre-set threshold value of an inhalation process parameter, that is different from the first pre-set threshold value , is underrun or exceeded during the inhalation process .26 . The inhalation device according to claim 25 , wherein the first signal is a first vibration signal of the inhalation device and or a first light signal and the second signal is a combination of a second vibration signal of the inhalation device that is stronger or different to the first vibration and a second light signal from the inhalation device , optionally whereinthe first and the second light signals comes from a top part of the inhalation device , which is made of translucent material through which the light signals are emitted .27 . The inhalation device according to claim 25 or 26 , wherein the control unit is further configured to control the signalling unit such that the signalling unit outputs the first s ignal if and whenever the first pre-set threshold value of an inhalation process parameter is exceeded during the inhalation and outputs the second signal if and whenever the second pre-set threshold value of an inhalation process parameter, that is higher than the first pre-set threshold value , is exceeded during the inhalation .28 . The inhalation device according to claim 27 , wherein the inhalation process parameter is the breath flow rate and optionally the tidal volume , and optionally wherein the first pre-set threshold of the breath flow rate is in the range of 30 1 / min or more preferably 40 1 / min or more to less than 75 1 / min and the second pre-set threshold of the breath flow rate is 75 1 / min or more .29 . The inhalation device according to any one of the preceding claims 25 to 28 , wherein the control unit is further configured to control the signalling unit to output a third signal if and whenever the inhalation device is not ready for use , optionally wherein the third signal is a combination of a third vibration signal of the inhalation device and a sound signal from the inhalation device .30 . The inhalation device according to any one of the preceding claims 25 to 29 , wherein the signalling unit comprises or consists of any one of the following accommodated within the inhalation device : means to generate an optical signal ; preferably a light signal , means to produce an acoustic signal ; preferably a sound signal and / or a voicesignal , means to produce a tactile signal ; preferably a vibration signal and an electronic display device .31 . An inhalation device system, comprising : an inhalation device , preferably the inhalation device as used in any one of claims 13 to 24 or the inhalation device according to any one of claims 25 to 30 and an electronic device that is different from and separate to the inhalation device , preferably a mobile phone , smartphone , smart watch, smart personal device or tablet computer , wherein both the inhalation device and the electronic device comprise communication means , configured to establish a wired or wireless communication connection between the inhalation device and the electronic device to exchange data on an inhalation process performed with the inhalation device .

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