WO2020120212A1

WO2020120212A1 - Humidification and mucus mobilization with an on-demand humidifier

Info

Publication number: WO2020120212A1
Application number: PCT/EP2019/083369
Authority: WO
Inventors: Pascal De Graaf; Marcel Mulder; Mareike Klee; Rita PRIORI
Original assignee: Koninklijke Philips N.V.
Priority date: 2018-12-11
Filing date: 2019-12-03
Publication date: 2020-06-18

Abstract

The invention relates to a device for providing an air stream and achieve mucous mobilization, wherein the device is configured to provide the air stream with a water or saline dose having a concentration between 12 and 18 mg/l.

Description

Humidification and Mucus Mobilization with an On-Demand Humidifier

FIELD OF THE INVENTION

The present invention relates to devices and methods for providing air streams to patients suffering from mucus related lung diseases. BACKGROUND OF THE INVENTION

Invasive mechanical ventilation always requires a humidifying system and for non-invasive ventilated patients a humidifier should be prescribed according to the patient’s symptoms.

For bedside or otherwise stationary use, patients with invasive and non- invasive ventilation use heated humidifiers (also known as pass-over humidifiers). While these provide sufficient humidification, they are not suitable for mobile use. For mobile use (either in the house or outside, while travelling, at school, etc.) patients are limited to humidification with a Heat-Moisture Exchanger (HME), which is either sub-optimal or not usable at all, causing a part of the patients to use no humidification at all.

For example invasive ventilated patients, not cuffed, with pressure ventilation have high need for humidification day and night to prevent trachitis. A HME is not effective for these patients and a pass over humidifier on a wheel chair is very risky and furthermore very power hungry, and therefore not suited for patients who want to be outside. The same situation holds for invasive ventilated patients, cuffed, with volumetric ventilation.

Non-invasive ventilated patients with mouthpiece ventilation have a strong need for humidification, since they have no respiration through the nose. For these patients a HME does not work, since patients exhale through the mouth and not the HME. These patients have a strong need for a portable, low power humidifier that gives sufficient humidification.

In addition, non-invasive ventilated patients in general have a strong need for a portable, low power humidifier, due to today’s higher flow pressure ventilation.

So all these patients are interested in a portable active humidification that offers sufficient humidification over day, when e.g. not at home for higher comfort and to prevent dry mouth and viscous mucus. In a small pilot study with 10 invasive ventilated patients, only 3 out of 10 participants use a HME for humidification over day. The 7 other patients do not have any humidification over day.

The 3 patients that used a HME indicate that the HME does not give sufficient humidification and that they would like to receive more humidification (Table 1).

Table 1: Preferences of patients using an HME in a 10 participant pilot study.

Another challenge for ventilated patients is the mobilization of viscous mucus. This mucus has to be removed frequently to avoid infections and blockages. A popular method to mobilize the mucus is to perform a‘broncheal cleansing' by instilling a vial (e.g. 5ml) of saline (0.9% NaCl) directly into the airway before performing removal techniques such as suctioning or cough-assist. This method is time consuming and unpleasant for the patient. To solve the issues of the patients, innovative solutions are required.

The device may injects a measured stream of aerosol in the ventilator circuit when the patient breathes in. The aerosol generating part (a mesh nebulizer) is located close to the patient to allow for a precise dose timing and therefore precise delivery. It can be used under all angles. The system does not have a hot water reservoir and does not have the risk of spilling hot water in the circuit. Additionally it is light weight and has a low power consumption (due to the air and water not being heated). Due to its low power and water consumption and safety the system fulfils the needs of the ambulatory ventilated patients.

Although the concept of using a timed nebulized for humidification is known from literature, due to the fundamentally different therapy delivery method (aerosol droplets instead of evaporated water molecules), nothing is known on the humidification that is needed and accepted by ventilated patients. Current guidelines on humidification ask for 33-44mg/L for heated pass over humidifiers and focus on the amount of water vapour needed in the air supplied to the patient. In order to prevent evaporation of water in the airway lining, the supplied air has to be saturated at body temperature (33-44mg/L). Humidifiers are therefore required to have a large vapour generating capability.

A direct translation of this guidelines to aerosol-based humidification cannot be made. The amount of water for humidification with nebulizers that is needed and acceptable by patients is not known.

SUMMARY OF THE INVENTION

Throughout the description, it is described that an air stream is provided with a water or saline dose having a certain concentration, defined in milligram per liter (mg/1). This means that per liter air a net addition of a certain amount (mg) of water or saline is added to the air stream.

In a first_aspect of the invention, a device for providing an air stream is presented. The device is configured to provide the air stream with a water or saline dose having a concentration below 18 mg/1, for example below 18 mg/1 and above 12 mg/1.

In an embodiment, the device comprises a ventilator for providing the air stream. An air hose is connected to the ventilator. The air hose is to be connected or coupled to the patient’s respiratory system. An aerosol generating part, e.g. a mesh nebulizer, may be located close to the patient to allow for a precise dose timing and therefore precise delivery.

This aerosol generating part adds the water or saline dose having a concentration below 18 mg/1 to the air stream generated by the ventilator. Thus, this dose is added to the air stream irrespective of the water or saline concentration of the provided air stream. This embodiment is also an embodiment of the third aspect of the invention.

According to an embodiment, the concentration is equal or below 12 mg/1, e.g below 12 mg/1 and above 6 mg/1.

According to an embodiment, the concentration is equal or below 6 mg/1, e.g. below 6 mg/1 and above a few mg/1.

According to an embodiment, the device is a portable device. As the provided doses are much lower than prior art indicated, this allows the skilled person to build or manufacture a portable device that is less bulky, lower cost and consumes less power.

According to an embodiment, the device comprises a nebulizer for providing the air stream with the dose. According to an embodiment, the nebulizer is a mesh nebulizer. It is an advantage that the mesh nebulizer allows better control over the generated droplet size. As described above, the nebulizer may be located close to the respiratory system of a patient using the device. This allows delivery of the correct dose to the patient without the disadvantage of loss of the dose inside the air hose, and optimal use of the inspiratory time to deliver the dose.

According to an embodiment, the device is configured such that the dose is provided only during the inhalation phase of the patient. According to an embodiment, the device may comprise one or more sensors for determining inhalation and exhalation phases of the patient. The sensor data may be used to activate the device, e.g. a nebulizer, to provide the water or saline dose to the air stream only when the patient inhales. It is an advantage of the invention that this allows precise control over the provided dose to the patient. This also contributes to portability of the device (less waste, so less liquid needs to be carried around).

In a second aspect of the invention, a method (therapy) for providing an air stream to a patient to increase the comfort of invasive and non- invasive ventilated patients is presented. The method comprises providing to the patient an air stream with a water or saline dose having a concentration below 18 mg/1, for example below 18 mg/1 and above 12 mg/1. This dose is added to the air stream irrespective of the concentration of the provided air stream.

According to an embodiment, the water or saline dose is added to the air stream using nebulization. According to an embodiment, mesh nebulization is used.

According to an embodiment, the water or saline dose is provided to the air stream only during the inhalation phase of the patient. The method may comprise a step of analyzing respiratory data from the patient and determining the inhalation phase of the patient and only provide the dose to the air stream when the patient is inhaling. It is an advantage of the invention that this allows precise control over the provided dose to the patient.

In a third_aspect of the invention, a device for providing an air stream and achieve mucous mobilization in a patient is presented. The device is configured to provide the air stream with a water or saline dose having a concentration between 12 and 18 mg/1. The surprising effect of this concentration is described in the detailed description section.

According to an embodiment, the device is configured to: provide the air stream with a water or saline dose having a concentration below 12 mg/1, e.g. below 12 mg/1 and above 6 mg/1; and thereafter provide the air stream with a water or saline dose having a concentration between 12 and 18 mg/1. As an advantage, it is no longer needed to

20 disconnect the patient interface to instill liquid, making for a less invasive and more comfortable therapy.

According to an embodiment, the device is a portable device.

According to an embodiment, the device comprises a nebulizer for providing the air stream with the dose.

According to an embodiment, the nebulizer is a mesh nebulizer.

According to an embodiment, the device is configured such that the dose is provided only during the inhalation phase of the patient. According to an embodiment, the device may comprise one or more sensors for determining inhalation and exhalation phases of the patient. The sensor data may be used to activate the device, e.g. a nebulizer, to provide the water or saline dose to the air stream only when the patient inhales. It is an advantage of the invention that this allows precise control over the provided dose to the patient. It further contributes to portability of the device (less waste, so less liquid needs to be carried around).

In a fourth_aspect, a method for providing an air stream to a patient to achieve mucous mobilization is presented. The method comprises providing the air stream with a water or saline dose having a concentration between 12 and 18 mg/1.

According to an embodiment, the method further comprises a step of providing the air stream with a water or saline dose having a concentration below 12 mg/1, e.g. below 12 mg/1 and above 6 mg/1, before the step of providing the air stream with a water or saline dose having a concentration between 12 and 18 mg/1. As an advantage, it is no longer needed to disconnect the patient interface to instill liquid, making for a less invasive and more comfortable therapy.

According to an embodiment, the patient is an invasively ventilated patient.

According to an embodiment, the water or saline dose is provided to the air stream only during the inhalation phase of the patient. The method may comprises a step of analyzing respiratory data from the patient and determining the inhalation phase of the patient and only provide the dose to the air stream when the patient is inhaling. It is an advantage of the invention that this allows precise control over the provided dose to the patient.

Particular and preferred aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims.

These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a graph representing an average level of comfort as indicated by the patients.

FIG. 2 shows a graph representing an average level of comfort as indicated by the patients, invasively ventilated and Non-invasively ventilated (NIV) patients.

FIG. 3 shows a graph representing an average level of comfort as indicated by the patients.

FIG. 4 shows a graph representing scores given to the degree of humidification perceived (efficacy).

FIG. 5 shows a graph representing an average score given to the degree of humidification perceived (efficacy).

FIG. 6 shows a graph representing an average score given to the degree of humidification perceived (efficacy), for Invasive and Non-Invasive.

FIG. 7 shows a graph representing an average start and stop values of objective patient data recorded during the study.

FIG. 8 shows a graph representing the number of mucus clearance events (suctions) before and after each dose, for individual patients and the average.

FIG. 9 shows a graph representing an average number of mucus clearance events (suctions) before and after each dose, for non- invasive and invasive ventilated patients.

DETAIFED DESCRIPTION OF THE EMBODIMENTS

In this invention a therapy is presented that uses a low power portable humidification to supply invasive and non- invasive ventilated patients sufficient and comfortable humidification at unexpectedly lower dose than included in guidelines. The main features are comfortable and effective humidification that have no effect on vital signs of the patients. The invented system has the further advantage that the dose can be adapted. At higher dose the system enables a comfortable mucus mobilization therapy. These therapies use essentially different doses of aerosolized diluted saline (0.005% NaCl). For these therapies, the diluted saline is provided by nebulization. The therapies can form a

complimentary overall therapy that involves constant humidification on the go and temporary mucus clearance sessions.

According to a first aspect of the invention, the invention is used for humidification. Based on literature on humidity in the respiratory system a computer model of the water losses at various points in the airway was built. This model indicated that the added dose of nebulized water should be no higher than 20mg/L, possibly lower, which is much lower than the humidification defined in the guidelines. For this reason, humidification with diluted saline was tested in the ranges of 6, 12 and 18mg/L. Exploration with patients for 120 to minutes at different doses unexpectedly showed that low doses of 6 mg/1 and 12 mg/ 1 are sufficient humidification therapy for invasive and non-invasive ventilated patients.

Participants were asked to rate the level of comfort after having received each dose for 120 minutes. The comfort was scored relative to normal daily humidification, which is either no humidification or HME. The score range was 0 (worse) to 10 (better) with 5 equal to normal daily humidification.

Table 2: Patient scoring of on-demand humidification dose As can be seen in Table 2, from the individual patient scoring, unexpectedly 80% of the patients give a high score for the low dose of 6 mg/ 1 (above 5), where only 10% score the dose 6 mg/1 equal and 10% lower than the daily therapy they use (no humidification or HME). As one can see, unexpect ly the patients prefer a much lower dose of 6 mg/1 for the on-demand humidification compared to the guidelines where 33 - 44 mg/1 are proposed, or even the 20mg/L predicted in our model. This unexpected result can be explained by the fact that for the nebulized humidification, only the moisture that is exhaled by during the exhalation phase needs to be replaced, whereas in pass-over humidification the supplied air needs to be completely saturated to avoid evaporation in the first place.

Furthermore, it unexpectedly was found that 70% of the patients score the slightly higher dose of 12 mg/ 1 high (above 5) where only 10% score the dose 12 mg/1 equal and 20% lower than the daily therapy they use (no humidification or HME).

Furthermore it was unexpectedly found that the slightly higher humidification dose of 18 mg/1 was only favourable scored for 2 out of 4 patients. For this reason, the higher dose of 18 mg/1 was not tested with all patients.

These findings clearly demonstrate that the nebulized humidification therapy can unexpectedly operate at much lower humidification doses of 6-12 mg/1 than indicated in the standard (33- 44 mg/ 1). This enables an active, portable, low power humidification therapy with high patient acceptance for invasive and non-invasive ventilated patients, which is with traditional humidification impossible.

Investigating the average scores of the patients, one can see that a low dose of humidification of around 6 mg/ 1 is unexpectedly preferred by patients. This is also shown in FIG. 1, with a trend to slightly higher score at 6 mg/ 1 compared to 12 mg/1. This trend is even more pronounced for non-invasive ventilated patients (

FIG. 2). A similar trend has been found for patients using an active circuit or a passive circuit, where the low dose of 6mg/l was highly scored by patients with an active circuit ( FIG. 3).

Please note, due to the limited patients in the study (10) no conclusions about statistical significance can be drawn.

Another metric that patients were asked to score is the efficacy, or the degree of humidification they perceived. FIG. 4 shows that 70% of the patients score the efficacy of humidification with 6mg/l higher than their standard therapy. 20% of the patients scored the experience of 12 mg/1 equal and 10% lower thatn the standard daily therapy. The dose of 18 mg/1 , which is still much lower than 33 -44 mg/1 in the standard, was unexpectedly score higher than the standard therapy by 2 patients but 2 patients scored this dose much lower.

FIG. 5 shows the average scores from the patients on the efficacy of the low dose 6 mg/1 and 12 mg/1 humidification, with a slight preference for 6mg/l.

This demonstrates that unexpectedly comfort and efficacy of nebulized humidification requires much lower doses of 6 - 12 mg/1, compared to humidification with pass over humidifiers, with a prescribed dose of 33-44 mg/1 in the guidelines.

This is similar for both invasive and non- invasive ventilated patients (

FIG. 6), with non-invasive ventilated patients scoring the efficacy higher on average. This indicated that the efficacy for both 6 and 12 mg/1 is perceived as equally good.

Also after patients have tested all doses (6 mg/ 1 , 12 mg/ 1 and 18 mg/ 1), and were asked to rescore each based on the total experience, 60% of the patients scored 6 mg/ 1 as most comfortable, 20% scored the dose 12 mg/ 1 as most comfortable and 20% could decide which was the most comfortable setting (see Table 3).

Patients in general gave high scores for the nebulized humidification compared to their normal daily humidification (either HME or nothing at all). 90% of the patients stated that on-demand humidification is an alternative to their normal daily humidification.

Table 3: Patient preference for dose (l=6mg/L, 2=12mg/L), compared to normal ambulatory humidification and potential of ODH as an alternative.

Exploration of the vital parameters of the patients have shown that this low dose nebulized humidification with 6 mg/ 1 and 12 mg/ 1 does not affect the vital parameters of the patients as measured for heart rate, respiratory rate, oxygen saturation (SpCh), transcutaneous carbon dioxide blood gas level (CO2) (F).

Based on these unexpected results, a therapy is invented that gives invasive and non- invasive ventilated patients sufficient and comfortable humidification in an ambulatory setting.

The therapy consists nebulization of liquid in such a way that all aerosol enters the patient, where the amount is measured with respect to the inhalation volume of the patient to achieve a net addition of 6mg , around 4 - 10 mg, of liquid per litre of air.

According to a second aspect of the invention, the invention is used for mucus mobilization. In this embodiment, a therapy is invented that supports patients in 2 ways: low- dose humidification in an ambulatory setting and mucous loosening. As in the first embodiment, the system delivers aerosolized water or saline or diluted saline, delivered during the inhalation. In normal use, for humidification, 4 - 10 mg/1 is delivered to the patient. When the patient need mucus loosening, the dose is increased to 12 - 18 mg/ 1 for a short period.

As FIG. 88 shows, the number of mucus clearance events increases significantly for the 12 and 18mg/l doses. The vital signs of the patients receiving 12mg/F are stable, indicating that this mobilization step is also safe for the patient. The increased mucus mobilization at higher dose nebulized humidification is used as therapy to replace the practice of saline instillation. The patient would be humidified with an ODH set at 6mg/l, and some time before a scheduled mucus clearance (e.g. 30 minutes), the dose in increased to 12mg/l. This way it is no longer needed to disconnect the patient interface to instil liquid, making for a less invasive and more comfortable therapy. An added benefit is the potential better overall mobilization thanks to the uniform deposition of the liquid, compared to the non-uniform deposition achieved with instillation.

This therapy could be especially of benefit for invasive ly ventilated patients, where as shown in FIG. 9, the number of suctions increased strongly.

The invention could be detected in aerosol-based humidifiers that deliver an effective dose between 0 and 12mg/L, and aerosol therapy devices aimed at humidification and mucus mobilization, which deliver a dose between 0 and 12mg/l for humidification and >12mg/L for mucus mobilization.

This invention can be applied to any aerosol based therapy device aimed at humidification or mucus mobilization. In order to ensure safety any device delivering this therapy must be able to control the delivered dose precisely, unlike that standard high volume bland aerosol generators can at this point. The ODH is capable of this, and so are other breath controlled nebulizers (some medicine inhalers).

As discussed above, the insight of low doses of water or saline solution being provided in an air stream delivered to the patient allows the build or manufacture of a low cost, portable and low power device.

Claims

CLAIMS:

1. A device for providing an air stream and achieve mucous mobilization, wherein the device is configured to provide the air stream with a water or saline dose having a concentration between 12 and 18 mg/1.

2. The device according to claim 1, wherein the device is configured to:

provide the air stream with a water or saline dose having a

concentration below 12 mg/1; and thereafter

provide the air stream with a water or saline dose having a

concentration between 12 and 18 mg/1.

3. The device according to any of the preceding claims, wherein the device is portable.

4. The device according to any of the preceding claims, further comprising a nebulizer for providing the air stream with the dose.

5. The device according to claim 5, wherein the nebulizer is a mesh nebulizer.

6. The device according to any of the preceding claims, wherein the device is configured such that the dose is provided only during the inhalation phase of the patient.

7. A method for providing an air stream to a patient to achieve mucous mobilization, comprising: provide the air stream with a water or saline dose having a concentration between 12 and 18 mg/1.

8. The method according to claim 7, further comprising a step of providing the air stream with a water or saline dose having a concentration below 12 mg/1 before the step of providing the air stream with a water or saline dose having a concentration between 12 and 18 mg/1.

9. The method according to any of claims 7-8 , wherein the patient is an invasively ventilated patient.

10. The method according to any of the claim 7-9, wherein the water or saline dose is added to the air stream using nebulization.

11. The method according to claim 10, wherein mesh nebulization is used.

12. The method according to any of claims 7-11, wherein the water or saline dose is provided to the air stream only during the inhalation phase of the patient.