Inhalable compositions

Abstract

The invention provides a liquid pharmaceutical composition comprising: a) at least one long-acting muscarinic receptor antagonist (LAMA) selected from the group consisting of glycopyrronium bromide, ipratropium bromide, umiclidium bromide, and revefenacin; b) at least one long-acting adrenoceptor agonist (LABA) selected from the group consisting of formoterol fumarate, salmeterol xinofoate; alformoterol tartarate, and vilanterol trifenate; and c) at least one inhaled corticosteroid (ICS) selected from the group consisting of beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, and fluticasone propionate; and wherein the composition is in the form of a solution for aerosolization, as well as methods and devices for use of the composition.

Description

[0001] TITLE: INHALABLE COMPOSITIONSDescription BACKGROUND OF THE INVENTION The present invention relates to the field of methods for the treatment and compositions for the use in the treatment of respiratory diseases or conditions, in particular pulmonary diseases and conditions, especially asthma and chronic obstructive pulmonary disease. Furthermore, the present invention relates to the field of inhalation devices or the administration of medically active liquids for inhalation therapy. More specifically, the present invention relates to the administration of a medically active liquid comprising a long- acting muscarinic receptor antagonist (LAMA), a long-acting adrenoceptor agonist (LABA); and an inhaled corticosteroid (ICS) by inhalation. Nebulizers or other aerosol generators for liquids are known from the art since a long time ago. Amongst others, such devices are used in medical science and therapy. There, they serve as inhalation devices for the application of active ingredients in the form of aerosols, i.e., small liquid droplets embedded in a gas. Such an inhalation device is known, e.g., from document EP 0627230 B1. Essential components of this inhalation device are a reservoir in which the liquid that is to be aerosolized is contained; a pumping device for generation of a pressure being sufficiently high for nebulizing; as well as an atomizing device in the form of a nozzle. By means of the pumping device, the liquid is drawn in a discrete amount, i.e., not continuously, from the reservoir, and fed to the nozzle. The pumping device works without propellant and generates pressure mechanically. WO 2018 / 197730 A1 discloses a soft mist inhalation device (SMI) having an impingement type nozzle which has proven to be useful for the effective administration of pharmaceutically active liquids especially in cases in which the medically active liquid or, more specifically, the pharmaceutically active compound or ingredient contained therein has to be administered to the lungs of the patient or other subject in need thereof. Asthma is a long-term inflammatory disease of the airways of the lungs, characterized by variable and recurring symptoms, reversible airflow obstruction and easily triggered bronchospasms. Symptoms include episodes of wheezing, coughing, chest tightness and shortness of breath. There is no known cure for asthma, but it can be controlled. Symptoms can be prevented by avoiding triggers, such as allergens and respiratory irritants, and suppressed with the use of inhaled corticosteroids. Long-acting adrenoceptor agonists (LABA) or antileukotriene agents may be used in addition to inhaled corticosteroids if asthma symptoms remain uncontrolled. Treatment of rapidly worsening symptoms is usually with an inhaled short- acting beta2 agonist such as salbutamol and corticosteroids taken by mouth. In very severe cases, intravenous corticosteroids, magnesium sulphate, and hospitalization may be required. Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms of COPD include shortness of breath and a cough, which may or may not produce mucus. COPD progressively worsens, with everyday activities such as walking or dressing becoming difficult. While COPD is incurable, it is preventable and treatable. Some therapies to manage asthma and / or COPD involve the inhalative administration of corticosteroids and / or Long-acting adrenoceptor agonists (LABA). Usually, the compositions are administered using pressurized metered dose inhalers (pMDI). It is an object of the present invention to provide new compositions and methods for an improved treatment and / or management of asthma and COPD. Further objects of the invention will be clear on the basis of the following description of the invention, examples and claims. DESCRIPTION OF THE DRAWINGS Figure 1 shows schematically one preferred embodiment of the inhalation device according to the invention prior to its first use. Figure 2 shows a device similar to the one of Fig.1, but without an outlet valve. Figure 3 shows the embodiment of Fig.1 with a filled pumping chamber. Figure 4 shows the situation during the first actuation of the device. Figure 5 shows the situation at the end of the first actuation. Figure 6 shows the situation after re-filling the pumping chamber. Figure 7 depicts the average droplet size distribution of a composition according to the invention administered via soft-mist inhaler. Figure 8 depicts the average droplet size distribution of a composition according to the invention administered via the Test Device with an ethanol cartridge. Figure 9 depicts a comparison of aerosol performance between Test Device and a pMDI (pMDI B / N: 1140705). Filled bars (lower portion) correspond to the delivered dose axis and the area of the bars shaded in dark grey corresponds to the fine particle fraction (FPF). Figure 10 depicts shot weight values for Test Device tested periodically over two days. DETAILED DESCRIPTION OF THE INVENTION The inventors developed an improved method and composition for the inhalative administration of a pharmaceutical composition comprising a combination of a long-acting muscarinic receptor antagonist, a long-acting adrenoceptor agonist and an inhaled corticosteroid. The composition developed by the inventors allows for administration as a solution and as such, can be administered using a soft-mist inhaler without the need for an additional propellant. Accordingly, in a first aspect, the invention relates to a liquid pharmaceutical composition comprising: a) at least one long-acting muscarinic receptor antagonist (LAMA); b) at least one long-acting adrenoceptor agonist (LABA); and c) at least one inhaled corticosteroid (ICS); wherein the composition is in the form of a solution for nebulization or atomization. Introductorily, some definitions of terms are given which are used throughout the description and claims. The definitions should be used to determine the meaning of the respective expressions unless the context requires a different meaning. ^Atomization^ and ^nebulization^ in the context of the present invention means the generation of fine, inhalable droplets of a liquid, in particular in the form of an aerosol. The typical dimensions of atomized droplets are in the range of several microns. An "aerosol" is a dispersion of a solid or liquid phase in a gas phase. The dispersed phase, also termed the discontinuous phase, is comprised of multiple solid or liquid particles. The aerosol generated by the inhalation device of the invention is a dispersion of a liquid phase in the form of inhalable liquid droplets in a gas phase which is typically air. The dispersed liquid phase may optionally comprise solid particles dispersed in the liquid. The term ^about^ or the like in connection with an attribute or value includes the exact attribute or precise value, as well as any attribute or value typically considered to fall within the normal or accepted variability associated with the technical field, and methods of measuring or determining said attribute or value. The term ^comprising,^ and related terms ^comprise^ or ^comprises^ would be understood as meaning that features additional to the features prefaced by the term may be present. Conversely, the term ^consists,^ and related terms would be understood as meaning that no other features, other than those prefaced by the term are present, and if present, only in trace or residual amounts such as to confer no technical advantage or relevance in respect of the object of the invention. For the avoidance of doubt, it should be noted that all embodiments and features of the present invention as well as combinations thereof as described below regardless of being referred to as ^specific^, ^particular^, ^preferred^, ^advantageous^ or in any other way may refer to all aspects of the present invention as summarized above and as additionally described below. The log acting muscarinic receptor antagonist is preferably selected from the group consisting of: glycopyrronium bromide,

[0002] umeclidium bromide, and revefenacin. A preferred long-acting muscarinic receptor antagonist is glycopyrronium bromide. In some embodiments of the invention, the liquid pharmaceutical composition comprises the at least one long-acting muscarinic receptor antagonist in a concentration of up to about 30 mg / mL. The long acting adrenoceptor agonist is preferably selected from the group consisting of:

[0003] arformoterol and

[0004] Vilanterol in free or pharmaceutically acceptable salt form. Preferably, the long-acting -adrenoceptor agonist (LABA) is selected from the group consisting of formoterol fumarate, salmeterol xinofoate; and alformoterol tartrate, and vilanterol trifenate. A preferred long acting adrenoceptor agonist is formoterol fumarate. The inhaled corticosteroid is preferably selected from the group consisting of beclomethasone dipropionate,

[0005] fluticasone furoate, and

[0006] fluticasone propionate. A preferred inhaled corticosteroid is beclomethasone dipropionate. The liquid pharmaceutical composition is characterized by being in the form of a solution at room temperature. Commonly, compositions comprising a combination of a long-acting muscarinic receptor antagonist, a long-acting adrenoceptor agonist and an inhaled corticosteroid are administered in the form of a suspension and require a propellant to be administered. In the context of the present invention, is a solution homogenous mixture of the compounds in a solvent, which is present in a single phase. The solvent may be a solution itself, e.g. a mixture of two solvents. The solution according to the invention does not comprise visible particles or other liquid phases. The liquid pharmaceutical composition according to the invention is in particular not a suspension or an emulsion. Particularly suitable solvents for the present invention are ethanol (EtOH) based. In some embodiments of the invention the liquid pharmaceutical composition is a solution comprising ethanol and optionally a further pharmacologically acceptable solvent or co-solvent, such as water. In some embodiments, the liquid pharmaceutical composition as defined above comprises at least 50 % EtOH (v / v). In some embodiments the liquid pharmaceutical composition comprises 50 % EtOH (v / v). In some embodiments the EtOH is the sole solvent of the liquid pharmaceutical composition, and all compounds are dissolved in EtOH. In some embodiments, the liquid pharmaceutical composition comprises 50 to 100 % (v / v) EtOH. In case the compounds are dissolved in less than 100% (v / v) EtOH it is preferred that the liquid pharmaceutical composition additionally comprises water. In some embodiments the liquid pharmaceutical composition according to the invention comprises at least 50 % (v / v), 60 % (v / v), 70 % (v / v), 75 % (v / v), 80 % (v / v), 90 %(v / v) or at least 100 % (v / v) EtOH. In some embodiments the liquid pharmaceutical composition comprises EtOH in a concentration of at least 90 % (v / v). In a particular embodiment the liquid pharmaceutical composition comprises 100 % (v / v) EtOH. Preferably, the liquid pharmaceutical composition comprises the compounds dissolved in a solvent, preferably in at least 50 % EtOH. The liquid pharmaceutical composition is suitable for inhalation and does not require a propellant. As such, in preferred embodiments, the liquid pharmaceutical composition according to the invention is free of a propellant, such as a hydrofluoroalkane (HFA) propellant. The components of the liquid pharmaceutical composition may be present in any suitable concentration, up to the solubility limit of the corresponding compound. As such, in some embodiments the at least one long acting muscarinic receptor antagonist is present in a concentration of up to about 30 mg / mL, or of from about 0.1 mg / mL to about 10 mg / mL or of from about 0.5 mg / mL to about 1.5 mg / mL, for example of about 1.0 mg / mL. In some embodiments the at least one long acting adrenoceptor agonist is present in a concentration of up to about 30 mg / mL, or of from about 0.05 mg / mL to about 10 mg / mL or of from about 0.1 mg / mL to about 1.0 mg / mL, for example of about 0.45 mg / mL. In some embodiments the at least one inhaled corticosteroid is present in a concentration of up to about 30 mg / mL, or of from about 1.0 mg / mL to about 20 mg / mL or , or from about 12.5 mg / mL to about 17.5 mg / mL, for example of about 14.3 mg / mL mg / mL to about 14.6 mg / mL. In some embodiments of the invention the liquid pharmaceutical composition comprises: a) the at least one long acting muscarinic receptor antagonist selected from the group consisting of glycopyrronium bromide, ipratropium bromide, umiclidium bromide, and revefenacin (which is preferably glycopyrronium bromide), in a concentration of up to about 30 mg / mL, or of from about 0.1 mg / mL to about 10 mg / mL or of from about 0.5 mg / mL to about 1.5 mg / mL, for example of about 1.0 mg / mL; b) at least one long acting adrenoceptor agonist selected from the group consisting of formoterol fumarate, salmeterol xinofoate; alformoterol tartrate, and vilanterol trifenate (which is preferably formoterol fumarate), in a concentration of up to about 30 mg / mL, or of from about 0.05 mg / mL to about 10 mg / mL or of from about 0.1 mg / mL to about 1.0 mg / mL, for example of about 0.45 mg / mL; and c) at least one inhaled corticosteroid selected from the group consisting of beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, and fluticasone propionate (which is preferably beclomethasone dipropionate), in a concentration of up to about 30 mg / mL, or of from about 1.0 mg / mL to about 20 mg / mL or , or from about 12.5 mg / mL to about 17.5 mg / mL, for example of about 14.3 mg / mL mg / mL to about 14.6 mg / mL. The pharmaceutical composition as defined above may additionally comprise one or more pharmaceutically acceptable excipients, which are suitable for inhalative use. Excipients which may be used in the liquid pharmaceutical composition include, but are not limited to, one or more buffering agents to regulate or control pH of the solution, chelating agents, salts such as sodium chloride, taste-masking agents, surfactants, lipids, antioxidants, and co- solvents, which may be used to enhance or improve solubility. Suitable excipients are known to the skilled person and are described, e.g., in standard pharmacopoeias such as U.S.P. or Ph. Eur., or in the Handbook of Pharmaceutical Excipients, 6th ed. Rowe et al, Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009. Exemplary compounds suitable as buffers for the adjustment of the pH of the present medically active liquid comprise, for example, sodium dihydrogen phosphate dihydrate and / or disodium hydrogen phosphate dodecahydrate, sodium hydroxide solution, basic salts of sodium, calcium or magnesium such as, for example, citrates, phosphates, acetates, tartrates, lactates etc., amino acids, acidic salts such as hydrogen phosphates or dihydrogen phosphates, especially those of sodium, moreover, organic and inorganic acids such as, for example, hydrochloric acid, sulphuric acid, phosphoric acid, citric acid, cromoglycinic acid, acetic acid, lactic acid, tartaric acid, succinic acid, fumaric acid, lysine, methionine, acidic hydrogen phosphates of sodium or potassium, etc., and further buffer systems as described above. In further specific embodiments, the medically active liquid to be nebulized and administered according to the present invention may comprise one or more further excipients which are selected from chelating agents, for example, disodium edetate dihydrate, calcium sodium EDTA, preferably disodium edetate dihydrate. In yet further specific embodiments, the medically active liquid to be nebulized and administered according to the present invention may comprise one or more preservatives and / or antioxidants. Suitable preservatives comprise but are not limited to benzalkonium chloride (BAC), parabens such as methylparaben, ethylparaben, propylparaben, sodium benzoate, sorbic acid and salts thereof. In specific embodiments, the medically active liquid to be nebulized and administered according to the present invention comprises benzalkonium chloride as a preservative. Suitable antioxidants comprise but are not limited to butylated hydroxytoluene (BHT), vitamin A, vitamin E, vitamin C, retinyl palmitate and others. Further excipients that may be included comprise, but are not limited to phoshatidylcholines, such as dilauroylphosphatidylcholine (DLPC), dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidyl glycerol (DTPA), diethylene triamine pentaacetic acid, hydrogenated soy phosphatidylcholine (HSPC), multilamellar vesicles, and soy phosphatidylcholine (SPC) such as Tween 80. In some embodiments, the liquid pharmaceutical composition is free of an excipient. In particular preferred embodiments, the liquid pharmaceutical composition consists of: a) at least one long-acting muscarinic receptor antagonist (LAMA); b) at least one long-acting adrenoceptor agonist (LABA); and c) at least one inhaled corticosteroid (ICS); d) EtOH; and optionally e) water; wherein the liquid pharmaceutical composition is in the form of a solution. In a particular embodiment of the invention, the liquid pharmaceutical composition consists of: a) at least one long acting muscarinic receptor antagonist (LAMA) selected from the group consisting of glycopyrronium bromide, ipratropium bromide, umiclidium bromide, revefenacin; b) at least one long-acting adrenoceptor agonist (LABA) selected from the group consisting of formoterol fumarate, salmeterol xinofoate; and alformoterol tartarate, vilanterol trifenate; c) at least one inhaled corticosteroid (ICS) selected from the group consisting of beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate; d) EtOH; and optionally e) water; wherein the liquid pharmaceutical composition is in the form of a solution. In a particular embodiment of the invention, the liquid pharmaceutical composition consists of: a) at least one long acting muscarinic receptor antagonist (LAMA) selected from the group consisting of glycopyrronium bromide, ipratropium bromide, umiclidium bromide, revefenacin in a concentration of about 0.5 to about 1.5 mg / mL; b) at least one long-acting adrenoceptor agonist (LABA) selected from the group consisting of formoterol fumarate, salmeterol xinofoate; and alformoterol tartrate, vilanterol trifenate in a concentration of about 0.1 mg / mL to about 1.0 mg / mL; c) at least one inhaled corticosteroid (ICS) selected from the group consisting of beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate in a concentration of about 5 mg / mL to about 15 mg / mL; d) at least 90 % (v / v) EtOH; and optionally e) water; wherein the liquid pharmaceutical composition is in the form of a solution. In one embodiment of the invention, the liquid pharmaceutical composition comprises: a) glycopyrronium bromide; b) formoterol fumarate; c) beclomethasone dipropionate; d) EtOH; and optionally e) water; wherein the liquid pharmaceutical composition is in the form of a solution. In some embodiments of the invention, the liquid pharmaceutical composition comprises: a) about 0.5 to about 1.5 mg / mL glycopyrronium bromide; b) about 0.1 mg / mL to about 1.0 mg / mL formoterol fumarate; c) about 5 mg / mL to about 15 mg / mL beclomethasone dipropionate; d) EtOH; and optionally e) water; wherein the liquid pharmaceutical composition is in the form of a solution. In one embodiment of the invention, the liquid pharmaceutical composition consists of: a) glycopyrronium bromide; b) formoterol fumarate; c) beclomethasone dipropionate; d) EtOH; and optionally e) water; wherein the liquid pharmaceutical composition is in the form of a solution. In some preferred embodiments of the invention, the liquid pharmaceutical composition consists of: a) about 0.5 to about 1.5 mg / mL glycopyrronium bromide; b) about 0.1 mg / mL to about 1.0 mg / mL formoterol fumarate; c) about 5 mg / mL to about 15 mg / mL beclomethasone dipropionate; d) at least 90% (v / v) EtOH; and optionally e) water; wherein the composition is in the form of a solution. In some embodiments of the invention, the liquid pharmaceutical composition consists of: a) about 0.5 to about 1.5 mg / mL glycopyrronium bromide; b) about 0.1 mg / mL to about 1.0 mg / mL formoterol fumarate; c) about 5 mg / mL to about 15 mg / mL beclomethasone dipropionate; and d) EtOH; wherein the composition is in the form of a solution. The liquid pharmaceutical compositions are suitable for use in the treatment and / or prevention of respiratory diseases and or conditions, preferably wherein the respiratory disease or condition is a pulmonary disease or condition, in particular asthma and chronic obstructive pulmonary disease (COPD). The liquid pharmaceutical composition is preferably administered by inhalation, in particular by inhalation using a soft-mist inhaler. Accordingly, in one aspect the invention relates to a liquid pharmaceutical composition as defined above, for use in a method of treatment and / or prevention of a respiratory disease or condition in a subject, preferably wherein the respiratory disease or condition is a pulmonary disease or condition, in particular for use in the treatment and / or prevention of asthma and / or COPD. In a further aspect, the invention relates to a method of treating and / or preventing a respiratory disease or condition in a subject, preferably wherein the respiratory disease or condition is a pulmonary disease or condition, in particular a method of treatment and / or prevention of asthma and / or COPD. In an additional aspect, the invention relates to the use of a liquid pharmaceutical composition as defined above in a method of treatment and / or prevention of a respiratory disease or condition in a subject, preferably wherein the respiratory disease or condition is a pulmonary disease or condition, in particular for use in the treatment and / or prevention of asthma and / or COPD. In an additional aspect, the invention relates to the use of a liquid pharmaceutical composition as defined above in the manufacture of a medicament for the treatment and / or prevention of a respiratory disease or condition in a subject, preferably wherein the respiratory disease or condition is a pulmonary disease or condition, in particular for use in the manufacture of a medicament for the treatment and / or prevention of asthma and / or COPD. The liquid pharmaceutical composition is preferably administered by inhalation or formulated for inhalation. In preferred embodiments, the invention relates to a liquid pharmaceutical composition for use in a method as defined above, wherein the liquid pharmaceutical composition is aerosolized and administered to a subject in need thereof, using an inhalation device. If administered by inhalation, the liquid pharmaceutical composition is preferably dispensed and / or administered in an amount of at least about 1µL, 2 µL, 5 µL, 10 µL, or 15 µL, or at least about 20 µL, 25 µL, 30 µL, or 50 µL, or from about 1 µL to about 50 µL or from about 2 µL to about 30 µL, or from about 5 µL to about 25 µL, or from about 10 µL to about 20 µL. In some embodiments the liquid pharmaceutical composition as defined above is dispensed and / or administered in an amount selected from of about 1 µL, 2 µL, 3 µL, 4 µL, 5 µL, 6 µL, 7 µL, 8 µL, 9 µL, 10 µL, 11 µL, 12 µL, 13 µL 14 µL, 15 µL, 16 µL, 17 µL, 18 µL, 19 µL and 20 µL. Administered by inhalation the liquid pharmaceutical composition is preferably administered as an aerosol with an average medium droplet size by volume (Dv50) of below 2.5 µm, specifically by a Dv50 of below 2.3 µL, which is well below the normally recognized Dv50 of 5 µm limit that is defined as within the inhalable range. In addition, the aerosol is administered to the patient with a spray duration of around 1.5-1.8 seconds which allows a more compliant administration of these complex formulations. Optionally, average medium droplet size by volume (Dv50) is assessed via droplet size distribution using laser diffraction, e.g. in accordance with Example 1. In a preferred embodiment, the pharmaceutical liquid pharmaceutical composition is dispensed or administered by an inhalation device and the liquid pharmaceutical composition comprises beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide and wherein one discrete dose of the aerosolized liquid pharmaceutical composition comprises beclomethasone dipropionate in an amount of from about 85 µg to about 90 µg, specifically of about 87 µg, formoterol fumarate in an amount of from about 4 µg to about 6 µg, specifically of about 5 µg and glycopyrronium bromide in an amount of from about 8 µg to about 10 µg, specifically of about 9 µg. In a further embodiment, , the liquid pharmaceutical composition is dispensed or administered by an inhalation device and the pharmaceutical composition comprises budesonide, formoterol fumarate and glycopyrronium bromide and wherein one discrete dose of the aerosolized liquid pharmaceutical composition comprises budesonide in an amount of from about 150 µg to about 170 µg, specifically of about 160 µg, formoterol fumarate in an amount of from about 4 µg to about 6 µg, specifically of about 4.8 µg and glycopyrronium bromide in an amount of from about 10 µg to about 12 µg, specifically of about 11 µg. Preferably, the inhalation device is a portable handheld inhalation device. The skilled person is aware of suitable inhalation devices. Suitable inhalation devices comprise soft-mist inhalers (SMIs). The term ^soft-mist-inhaler^ as used herein, in specific embodiments, refers to a preferably non-electrified mobile inhalation device for liquid formulations with low velocity nebulization properties. In further specific embodiments, such inhalation device or, more specifically, such soft-mist inhaler comprises at least one impingement-type nozzle as described in further detail below for the nebulization / aerosolization of the medically active liquid. Soft-mist inhalers as described above have been proven as a very effective means for providing medically active liquids or compositions or pharmaceutically active compounds contained therein into the lung of a patient or subject in need thereof. A soft-mist inhaler as referred to herein typically comprises one or a plurality of impingement-type nozzles. Such an impingement-type nozzle is adapted to emit at least two jets of liquid which are directed such as to collide and break up into small aerosol droplets, thereby generating an aerosol of the medically active liquid in nebulized or aerosolized form. Especially in the case of hand- held nebulizers the nozzle or nozzles usually are firmly affixed to the user-facing side of the housing of the inhalation device in such a way that it is immobile, or non-moveable, relative to the housing or at least relative to the side or part of the housing which faces the user (e.g., patient) when the device is used. Other suitable inhalation devices are known such as, e.g., the Respimat® inhaler (Boehringer Ingelheim), vibrating membrane nebulizers such as eFlow® (PARI), Vibrating-Mesh® nebulizers (such as Philips InnoSpire Go) and others. Preferred inhalation devices comprise a mechanical pumping unit adapted to pressurize and convey the liquid pharmaceutical composition. In preferred embodiments, said pumping unit is adapted to pressurize the liquid pharmaceutical composition to a pressure of at least 50 bar, specifically to a pressure within the range of from about 100 to about 250 bar. In particular, a preferred inhalation device comprises a pressure cylinder and a piston reciprocally movable within the pressure cylinder. Said piston may be a hollow piston comprising a liquid channel through which the liquid pharmaceutical composition is conveyed. In a specific embodiment, said piston is adapted to be in a fixed position and the pressure cylinder is adapted to be movable during operation of the pumping unit. The inhalation device comprises at least one nozzle suitable or adapted for aerosolization of the liquid pharmaceutical composition as defined above. In some embodiments, said at least one nozzle is an impingement-type nozzle comprising at least two ejection channels through which at least two streams of the liquid pharmaceutical composition are ejected. Preferably, the at least two ejection channels are adapted to generate the at least two streams of the liquid pharmaceutical composition such that at least two of the at least two liquid streams collide in a collision point thereby aerosolizing the liquid pharmaceutical composition. A further exemplary suitable inhalation device is known, e.g., from document EP 0627230 B1, the contents of which are incorporated herein by reference in its entirety. Essential components of this exemplary inhalation device are a reservoir in which the medically active liquid that is to be aerosolized is contained; a pumping device for generation of a pressure being sufficiently high for nebulizing; as well as an atomizing device in the form of a nozzle. By means of the pumping device, the liquid is drawn in a discrete amount, i.e., not continuously, from the reservoir, and fed to the nozzle. The pumping device works without propellant and generates pressure mechanically. Accordingly, in specific embodiments a preferred inhalation device to be used in the context of the present invention works without a propellant. In further specific embodiments, the pressure of the medically active liquid to be dispensed is generated mechanically, such as by the force of a spring. A further exemplary embodiment of a suitable inhalation device is described in document WO 91 / 14468 A1, the contents of which are herein incorporated by reference in its entirety. In such a device, the pressure in the pumping chamber which is connected to the housing is generated by movement of a moveable hollow piston. The piston is moveably arranged inside the immobile cylinder or pumping chamber. The (upstream arranged) inlet of the hollow piston is fluidically connected to the interior of the reservoir (reservoir pipe section). Its (downstream arranged) tip leads into the pumping chamber. Furthermore, a check valve that inhibits a back flow of liquid into the reservoir is arranged inside the tip of the piston. A specific embodiment of such a soft mist inhaler which is suitable for the administration of the liquid pharmaceutical composition as described above is described, e.g., in international patent application WO 2018 / 197730 A1, the contents of which are incorporated herein by reference in its entirety. It should be noted, however, that the inhaler device described therein is just one example of a suitable inhaler device to be used according to the present invention and, therefore should not be interpreted as limiting the scope of the invention in any respect. In a particular embodiment, the inhalation device is a hand-held inhalation device comprising (a) a housing (1) having a user-facing side; (b) an impingement-type nozzle (6) for generating the nebulised aerosol by collision of at least two liquid jets, the nozzle (6) being firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); (c) a fluid reservoir (2) arranged within the housing (1); and (d) a pumping unit arranged within the housing (1), the pumping unit having - an upstream end that is fluidically connected to the fluid reservoir (2); - a downstream end that is fluidically connected to the nozzle (6); wherein the pumping unit is adapted for pumping fluid (F) from the fluid reservoir (2) to the nozzle (6); wherein the pumping unit further comprises (i) a riser pipe (5) having an upstream end, wherein the riser pipe (5) is - adapted to function as a piston in the pumping unit, and - firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); and (ii) a hollow cylinder (9) located upstream of the riser pipe (5), wherein the upstream end of the riser pipe (5) is inserted in the cylinder (9) such that the cylinder (9) is longitudinally movable on the riser pipe (5); (iii) a lockable means for storing potential energy (7) when locked and for releasing the stored energy when unlocked, the means (7) being arranged outside of, and mechanically coupled to, the cylinder (9) such that unlocking the means (7) results in a propulsive longitudinal movement of the cylinder (9) towards the downstream end of the pumping unit. The above reference numerals correspond to Figures 1-6. Such a preferred inhalation device is referred to as the ^Test Device^ in the examples. Such a preferred inhalation device comprises a housing having a user-facing side, an impingement-type nozzle for generating the nebulized aerosol by collision of at least two liquid jets, a fluid reservoir arranged within the housing, and a pumping unit which is also arranged within the housing. In these preferred embodiments, the nozzle may be firmly affixed to the user-facing side of the housing such as to be immobile relative to the housing. The pumping unit may have an upstream end that is fluidically connected to the fluid reservoir and a downstream end that is fluidically connected to the nozzle, whereas in the context of the present invention an ^upstream^ direction or position means a position or direction from which the medically active liquid is conveyed, and a ^downstream^ direction or position means a position or direction to which the medically active liquid is conveyed or in other words in the direction of the nozzle. Furthermore, the pumping unit may be adapted for pumping fluid from the fluid reservoir to the nozzle, and it may comprise a riser pipe which is adapted to function as a piston in the pumping unit, a hollow cylinder and a lockable means for storing potential energy. The riser pipe may be firmly affixed to the user-facing side of the housing such as to be immobile relative to the housing. The hollow cylinder may be located upstream of the riser pipe, and the upstream end of the riser pipe may be inserted in the cylinder such that the cylinder is longitudinally movable on the riser pipe. The lockable means typically is capable of storing potential energy when locked and adapted for releasing the stored energy when unlocked. The means may be arranged outside of, and mechanically coupled to, the cylinder in such a way that unlocking the means results in a propulsive longitudinal movement of the cylinder towards the downstream end of the pumping unit. As used herein, a ^hand-held^ inhalation device is a mobile inhalation device which can be conveniently held in one hand (preferably by the user but also by another person) and which is suitable for delivering a nebulized medically active aerosol for inhalation therapy. In order to be suitable for inhalation therapy, the device must be able to emit a medically active aerosol, namely the medically active liquid of the present invention in nebulized form, whose particle or, more specifically, droplet size is respirable, i.e., small enough to be taken up by the lungs of a patient or user. Typically, respirable particles have a diameter as measured by laser diffraction of not more than about 10 µm, in particular not more than about 7 µm, or not more than about 5 µm, respectively. In this respect, inhalation devices suitable for the administration of the medically active liquid in nebulized form according to the present invention are also substantially different from devices that emit spray for oral or nasal administration, such as disclosed in US 2004 / 0068222 A1. In some embodiments, the inhalation device is adapted to aerosolize the liquid pharmaceutical composition to form an aerosol with an average medium droplet size by volume (Dv50) of below 2.5 µm, specifically by a Dv50 of below 2.3 µm. The inhalation device is further preferably adapted for a spray duration of around 1.5-1.8 seconds which allows a more compliant administration of these complex formulations. The inhalation device that may be used according to the present invention is capable of delivering a nebulized aerosol of the liquid pharmaceutical composition as defined above. As used herein, an aerosol is a system having at least two phases: a continuous phase which is gaseous, and which comprises a dispersed liquid phase in the form of small liquid droplets. Optionally, the liquid phase may itself represent a liquid solution, dispersion, suspension, or emulsion. In specific embodiments, the gaseous phase of the medically active liquid in aerosolized form according to the present invention is air or another physiologically acceptable gas or a mixture thereof, preferably air. Important for the generation of a nebulized aerosol is a suitable nozzle. According to specific embodiments of the invention, the nozzle of preferred inhalation devices, specifically soft mist inhalers, is of the impingement type. This means that the nozzle is adapted to emit at least two jets of the medically active liquid which are directed such as to collide and break up into small aerosol droplets. The nozzle may be firmly affixed to the user-facing side of the housing of the inhalation device in such a way that it is immobile, or non-moveable, relative to the housing or at least relative to the side or part of the housing which faces the user (e.g., patient) when the device is used. The fluid reservoir of the specific hand-held inhalation device as described above which is typically arranged within the housing may be adapted to hold or store the composition from which the nebulized aerosol is generated and delivered by the inhalation device. The pumping unit of the specific inhalation device which is also arranged within the housing may be adapted to function as a piston pump, also referred to as plunger pump, wherein the riser pipe may function as the piston, or plunger, which is longitudinally moveable within the hollow cylinder. In this embodiment, the inner segment of the hollow cylinder in which the upstream end of the riser pipe moves forms a pumping chamber which has a variable volume, depending on the position of the riser pipe relative to the cylinder. The hollow cylinder of the preferred inhalation device which provides the pumping chamber is fluidically connected with the fluid reservoir, either directly or indirectly, such as by means of an optional reservoir pipe (or reservoir pipe section). Similarly, the riser pipe, whose reservoir-facing, interior (upstream) end which can be received in the hollow cylinder, is fluidically connected at its downstream or exterior end to the nozzle in a liquid-tight manner, either directly or indirectly. In this context, the expression ^hollow cylinder^ as used herein refers to a part or member which is hollow in the sense that it comprises an internal void which has a cylindrical shape, or which has a segment having a cylindrical space. In other words, and as is applicable to other types of piston pumps, it is not required that the external shape of the respective part or member is cylindrical. Moreover, the expression ^hollow cylinder^ does not exclude an operational state of the respective part or member in which the ^hollow^ space may be filled with material, e.g., with a liquid to be nebulized. As used herein, a ^longitudinal movement^ is a movement along the main axis of the hollow cylinder, and a propulsive movement is a movement of a part in a downstream (or forward) direction. Importantly, the riser pipe of the pumping unit of the preferred hand-held inhalation device is arranged downstream of the cylinder, and it is firmly affixed to the user-facing side of the housing such as to be immobile relative to the housing or at least to the part of the housing which comprises the user-facing side of the housing. For the avoidance of doubt, the term ^firmly fixed^ as used herein means either directly or indirectly (i.e., via one or more connecting parts) fixed such as to prevent relative movement between the respective parts. As in the preferred inhalation device as described above the nozzle is also immobile relative to the housing or the respective part of the housing, the riser pipe is also immobile relative to the nozzle, and the pumping action is affected by the longitudinal movement of the hollow cylinder. A propulsive movement of the cylinder, which is arranged in an upstream position relative to the riser pipe, results in a decrease of the volume of the pumping chamber, and a repulsive movement of the cylinder results in an increase of the volume. In other words, in the preferred hand-held inhalation device the riser pipe maintains its position relative to the housing, and the hollow cylinder can alter its position relative to the housing, and in particular, along a longitudinal axis of the same, such as to perform a piston-in-cylinder-type movement of the immobile riser pipe in the moveable cylindrical member. This arrangement differs from other impingement-type inhalation devices which rely on a pumping unit whose riser pipe is in an upstream position and a cylindrical member in a downstream position wherein the riser pipe is moveable and the cylindrical member is fixed to the housing, as disclosed in US 2012 / 0090603 A1. For the avoidance of doubt, however, it should be noted that in specific embodiments these inhalation devices may also be used to nebulize the medically active liquid according to the present invention. A key advantage of the described preferred inhalation device is that the passage between pumping chamber and fluid reservoir can be designed with less restrictions with respect to its dimensions. It is e.g., possible to accommodate a significantly larger inlet valve (also referred to as check valve), which is easier to manufacture since it does not have to be contained within a narrow riser pipe. Instead, the invention allows the use of a check valve whose size is only restricted by the interior size of the housing or the dimensions of the means for storing potential energy. In other words, the diameters of the valve, the riser pipe and ^ if used ^ the reservoir pipe do not need to match each other. Furthermore, since no movable piston needs to be connected to the fluid reservoir, the component which provides the fluid connection to the reservoir can be designed independently of the moveable component, i.e., the hollow cylinder, allowing the individual parts to be adapted to suit their respective individual functions. In this respect, the preferred inhalation device as described above provides for higher design flexibility because the moveable hollow cylinder, due to its robust structure and dimensions, provides better opportunities for designing a mechanically stable connection with the reservoir than would a less robust moveable riser pipe. Also, the connection between the hollow cylinder and the fluid reservoir can be designed with a larger diameter, such that higher flow velocities and fluid viscosities become feasible. Further, a support for the reservoir can be integrated into any component that comprises the cylinder. Additionally, any vent for pressure equilibration of the reservoir can be moved away from the reservoir body itself to (e.g.) a connector which forms an interface between reservoir and hollow cylinder, thus facilitating construction and avoiding the necessity to provide an essentially ^open^ reservoir body. As already mentioned, the lockable means for storing potential energy of the preferred inhalation device is adapted to store energy in its locked state and to release the stored energy when unlocked. In specific embodiments, the lockable means is mechanically coupled to the hollow cylinder in such a way such that unlocking the means results in a propulsive longitudinal movement of the cylinder towards the downstream end of the pumping unit. During this movement, the internal volume of the cylinder, i.e., the volume of the pumping chamber, decreases. Vice versa, when the means for storing potential energy is in the locked state, the hollow cylinder is in its most upstream position in which the volume of the pumping chamber is largest. The locked state could also be considered a primed state. When the state of the means for storing energy is altered from the unlocked to the locked state, which could be referred to as priming the device, the hollow cylinder performs a repulsive longitudinal movement, i.e., from its most downstream position towards its most upstream position. A pumping cycle of the preferred inhalation device as described above consists of two subsequent and opposing movements of the cylinder starting from its most downstream position to its most upstream (or primed) position and ^ driven by the means for storing potential energy that now releases its energy ^ back to its most downstream position. In specific embodiments, the inhalation device suitable for the generation of the medically active liquid in nebulized form according to the present invention is capable, especially in the case of inhalation device having an impingement-type nozzle is capable of pressurizing the medically active liquid to be nebulized to a pressure of up to 1,000 bar (one thousand bar), such as from about 2 bar to about 500 bar or to about 300 bar or from about 50 bar to about 250 bar. In specific embodiments of the preferred inhalation device as described above, the pumping unit is a high-pressure pumping unit and adapted to operate, or to expel fluid, at a pressure of at least about 50 bar. In other preferred embodiments, the operating pressure of the pumping unit is at least about 10 bar, or at least about 100 bar, or from about 2 bar to about 1,000 bar, or from about 50 bar to about 250 bar, respectively. As used herein, the ^operating^ pressure is the pressure at which the pumping unit expels fluid, in particular the medically active liquid comprising an inhalable corticosteroid, from its pumping chamber in a downstream direction, i.e., towards the nozzle. In this context, the expression ^adapted to operate^ means that the components of the pumping unit are selected with respect to the materials, the dimensions, the quality of the surfaces and the finish are selected such as to enable operation at the specified pressure. Moreover, such high-pressure pumping unit implies that the means for storing potential energy preferably is capable of storing and releasing a sufficient amount of energy to drive the propulsive longitudinal movement of the cylinder with such a force that the respective pressure is obtained. For example, in the preferred inhalation device as described herein the means for the storage of potential energy may be designed as tension or pressure spring. Alternatively, besides a metallic or plastic body, also a gaseous medium, or magnetic force utilizing material can be used as means for energy storage. By compressing or tensioning, potential energy may be fed to the means. One end of the means may be supported at or in the housing at a suitable location; thus, this end is essentially immobile. With the other end, it may be connected to the hollow cylinder which provides the pumping chamber; thus, this end is essentially moveable. The means can be locked after being loaded with a sufficient amount of energy, such that the energy can be stored until unlocking takes place. When unlocked, the means can release the potential energy (e.g. spring energy) to the cylinder with the pumping chamber, which is then driven such as to perform a (in this case, longitudinal) movement. Typically, the energy release takes place abruptly, so that a high pressure can build up inside the pumping chamber before a significant amount of liquid is emitted, which results in a pressure decrease. In the preferred inhalation device as described above, during a significant portion of the ejection phase, an equilibrium exists of pressure delivered by the means for the storage of potential energy, and the amount of already emitted liquid. Thus, the amount of liquid remains essentially constant during this phase, which is a significant advantage to devices which use manual force of the user for the emission, such as the devices disclosed in documents US 2005 / 0039738 A1, US 2009 / 0216183 A1, US 2004 / 0068222 A1, or US 2012 / 0298694 A1, since manual force depends on the individual user or patient and is very likely to vary largely during the ejection phase, resulting in inhomogeneous droplet formation, size, and amount. In contrast to these devices, the means according to the preferred inhalation device as described above in connection with the present invention ensures that the inhalation device delivers highly reproducible results. The means for storing potential energy may also be provided in the form of a highly pressurized gas container. By suitable arrangement and repeatable intermittent activating (opening) of the same, part of the energy which is stored inside the gas container can be released to the cylinder. This process can be repeated until the remaining energy is insufficient for once again building up a desired pressure in the pumping chamber. After this, the gas container must be refilled or exchanged. In one of the preferred embodiments, the means for storing potential energy comprised by the inhalation device that may be used in the context of the present invention is a spring having a load of at least 10 N in a deflected state. In a particularly preferred embodiment, the means for storing potential energy is a compression spring made of steel having a load from about 1 N to about 500 N in its deflected state. In other preferred embodiments, the compression spring from steel has a load from about 2 N to about 200 N, or from about 10 N to about 100 N, in its deflected state. The inhalation device that may be used in connection with the present invention is preferably adapted to deliver the nebulized composition in a discontinuous manner, i.e., in the form of discrete units, wherein one unit is delivered per pumping cycle. In this aspect, suitable inhalation devices differ from commonly known nebulizers such as jet nebulizers, ultrasonic nebulizers, vibrating mesh nebulizers, or electrohydrodynamic nebulizers which typically generate and deliver a nebulized aerosol continuously over a period of several seconds up to several minutes, such that the aerosol requires a number of consecutive breathing manoeuvres in order to be inhaled by the patient or user. Instead, a preferred inhalation device of the invention is adapted to generate and emit discrete units of aerosol, wherein each of the units corresponds to the amount (i.e., volume) of fluid (i.e., medically active liquid) which is pumped by the pumping unit in one pumping cycle into the nozzle where it is immediately aerosolized and delivered to the user or patient. Vice versa, the amount of liquid pumped by the pumping unit in one pumping cycle determines the amount of the pharmacologically active agent which the patient receives per dosing. It is therefore highly important with respect to achieving the desired therapeutic effect that the pumping unit operates precisely, reliably and reproducibly. The inventors have found that especially the preferred inhalation device as described above incorporating the pumping unit as described above is particularly advantageous in that it does exhibit high precision and reproducibility. In one preferred embodiment, a single dose of the medication is contained in one unit, i.e., in the volume that is delivered from the pumping unit to the nozzle for aerosol generation in one single pumping cycle. In this case, the user or patient will prime and actuate the inhalation device only once, and inhale the released aerosol in one breathing manoeuvre, per dosing (i.e., per dosing event). In preferred embodiments, one discrete dose of the aerosolized liquid pharmaceutical composition comprises from about 9 mg to about 13 mg, or from about 10.5 mg to about 11.5 mg of the aerosolized liquid pharmaceutical composition. The volume of medically active liquid that is pumped by the pumping unit in one pumping cycle is preferably in the range from about 2 to about 150 µl. In particular, the volume may range from about 0.1 µL to about 1,000 µL (one thousand µL), or from about 1 µL to about 250 µL or from about 1 µL to about 100 µL, or from about 2 µL to about 50 µL, or from about 5 µL to about 25 µL, or from about 10 µL to about 20 µL. In some embodiments the liquid pharmaceutical composition as defined above is dispensed and / or administered in an amount selected from of about 1 µL, 2 µL, 3 µL, 4 µL, 5 µL, 6 µL, 7 µL, 8 µL, 9 µL, 10 µL, 11 µL, 12 µL, 13 µL 14 µL, 15 µL, 16 µL, 17 µL, 18 µL, 19 µL and 20 µL. These volume ranges are nearly the same as the volume of liquid phase that is contained in one unit of aerosol generated by the inhalation device, perhaps with minor differences due to minute losses of liquid in the device. In another preferred embodiment of the preferred inhalation device as described above, the pumping unit comprises an inlet valve, also referred to as a check valve or inlet check valve, positioned in the hollow cylinder. According to this embodiment, the interior space of the hollow cylinder, i.e., the pumping chamber, is fluidically connected with the fluid reservoir via the inlet check valve. The inlet valve allows the inflow of liquid into the pumping chamber, but prevents the backflow of liquid towards, or into, the fluid reservoir. The position of the inlet valve may be at or near the upstream end of the cylinder such as to make nearly the entire internal volume of the hollow cylinder available for functioning as the pumping chamber. Alternatively, it may be more centrally located along the (longitudinal) main axis of the hollow cylinder such as to define an upstream segment and a downstream segment of the cylinder, the upstream segment being upstream of the inlet valve and the downstream segment being downstream of the valve. In this case the pumping chamber is located in the downstream segment. As mentioned, one of the advantageous effects is that an inlet valve having relatively large dimensions may be accommodated in this position, i.e., at the upstream end of the pumping chamber. This is particularly beneficial as it allows for large dimensions of the fluid conduit(s) within the valve, thus enabling high fluid velocities which translate into a rapid filling of the pumping chamber during the priming of the inhalation device. Moreover, the use of liquids having a higher viscosity than ordinary liquid formulations for inhalation, such as highly concentrated solutions of soluble active ingredients, become feasible for inhalation therapy. According to a further preferred embodiment, the inlet valve is adapted to open only when the pressure difference between the upstream and the downstream side of the valve, i.e., the fluid reservoir side and the pumping chamber side, is above a predefined threshold value, and remains closed as long as the pressure difference is below the threshold value. The term ^pressure difference^ as used in that context means that, irrespective of the absolute pressure values, only the relative pressure difference between the two sides is relevant for determining whether the valve blocks or opens. If, for example, the pressure on the upstream (reservoir) side is already positive (e.g., 1.01 bar due to thermal expansion), but the pressure on the downstream (pumping chamber) side is ambient pressure (1.0 bar, no activation of the device), the pressure difference (here: 0.01 bar) is below the threshold value (e.g., 20 mbar), which allows the valve to stay closed even when subject to a positive pressure in opening direction. This means that the check valve remains closed until the threshold pressure is met, thus keeping the passage between reservoir and pumping chamber safely shut e.g., when the inhalation device is not in use. Examples for threshold pressure differences are in the range of 1 to 1,000 mbar, and more preferably between about 10 and about 500 mbar, or between about 1 and about 20 mbar. When actuating the above-described inhalation device, as the means for storing potential energy alters its state from a locked state to an unlocked state, energy is released which effects the cylinder to perform its propulsive longitudinal movement, significant pressure is built up in the pumping chamber. This generates a marked pressure difference (due to a high pressure in the pumping chamber and a substantially lower pressure in the fluid reservoir) which exceeds the threshold value of the pressure difference, so that the check valve opens and allows the pressure chamber to become filled with liquid from the reservoir. A valve type that may be designed to operate with such a threshold pressure difference is a ball valve pre-loaded with a spring. The spring pushes the ball into its seat, and only if the pressure acting against the spring force exceeds the latter, the ball valve opens. Other valve types which ^ depending on their construction ^ may operate with such a threshold pressure difference are duckbill valves or flap valves. The advantage of such a valve operating with a threshold pressure difference is that the reservoir can be kept closed until active use is being made of the inhalation device, thus reducing unwanted splashing of reservoir liquid during device transport, or evaporation during long-term storage of the device. In a further preferred embodiment, the inhalation device that may be preferably used in the context of the invention further comprises an outlet valve inside the riser pipe, or at an end of the riser pipe, for avoiding a return flow of liquid or air from the riser pipe into the hollow cylinder. In many cases, the use of such outlet valve will prove to be advantageous. Typically, the downstream end of the riser pipe is located close to the nozzle. The nozzle is in fluidic communication with the outside air. After emitting, in aerosolized form, the amount of liquid which is delivered from the pumping unit through the nozzle, driven by the propulsive longitudinal movement of the cylinder, the pumping chamber must be refilled. For this purpose, it slides back on the riser pipe into its previous upstream position (i.e., performs a repulsive longitudinal movement), so that the interior volume of the pumping chamber increases. Along with this, a negative pressure (sometimes also referred to as ^underpressure^) is generated inside the pumping chamber which causes liquid to be sucked into the pumping chamber from the fluid reservoir which is located upstream of the pumping chamber. However, such negative pressure may also propagate downstream through the riser pipe up to the outside of the nozzle and could lead to air being sucked into the device through the nozzle, or nozzle openings, respectively. This problem can be avoided by providing an outlet valve, also referred to as outlet check valve, which opens towards the nozzle openings and blocks in the opposite direction. Optionally, the outlet valve is of a type that blocks below (and opens above) a threshold pressure difference as described in the context of the inlet valve above. If a ball valve with a spring is used, the spring force must be directed against the pumping chamber such that when the difference between the interior pressure of the pumping chamber and the ambient pressure exceeds the threshold pressure difference value, the outlet valve opens. The advantages of such a valve correspond to the respective aforementioned advantages. As mentioned, the outlet valve may be positioned within the riser pipe. Alternatively, the inhalation device may comprise an outlet valve which is not integrated within the riser pipe but positioned at or near one of the ends of the riser pipe, in particular at or near its downstream end, e.g., in a separate connector between the riser pipe and the nozzle. This embodiment may be advantageous in certain cases, e.g., if there is a need for a riser pipe with a particularly small diameter which makes the integration of a valve difficult. By accommodating the outlet valve downstream of the riser pipe, a valve with a relatively large diameter may be used, thus simplifying the requirements for the valve design. In a further alternative embodiment, the outlet valve is absent. This embodiment may be feasible as the fluid channels of an impingement-type nozzle may have relatively small cross sections, resulting in only minor or very slow back flow at the given pressure conditions during the priming of the device. If the amount of backflow is considered acceptable in view of a particular product application, the inhaler design may be simplified by avoiding the outlet valve. In any case, whether the inhalation device is designed with or without an outlet valve, all other options and preferences described with respect to other device features are applicable to both of these alternative embodiments. In a further preferred embodiment, the inhalation device that may be used in the context of the present invention comprises a fluid reservoir which is firmly attached to the hollow cylinder such as to be moveable together with the hollow cylinder inside the housing. This means that in each ejection phase of the pumping cycle, the fluid reservoir moves together with the hollow cylinder from an initial (^upstream^) position, in which the pumping chamber has its maximum interior volume, towards an end (^downstream^) position, in which the volume of the pumping chamber is minimal; and during the subsequent ^priming^ step, the fluid reservoir returns together with the hollow cylinder to their initial (^upstream^) position. As used herein, the expression ^firmly attached^ includes both permanent and non- permanent (i.e., releasable) forms of attachment. Moreover, it includes direct and indirect (i.e., via one or more connecting parts) types of attachment. At the same time, as mentioned above, ^firmly attached^ means that the respective parts are fixed to each other in such a way as to substantially prevent their movement relative to each other. In other words, two parts that are firmly attached to each other may only be movable together, and with respect to each other, they are non-movable or immobile. One of the advantages of this embodiment wherein the fluid reservoir is firmly attached to the hollow cylinder is that it provides the smallest possible dead volume between the reservoir and the pumping chamber. According to an alternative embodiment, the fluid reservoir may be fluidically connected to the hollow cylinder by means of a flexible tubular element, and firmly attached to the housing. According to this embodiment, the reservoir is not firmly attached to the hollow cylinder and does not move along with it when the cylinder performs its longitudinal movements. Instead, it is firmly, but optionally detachably, directly or indirectly, attached to the housing or to a part of the housing. One advantage of this embodiment is that the energy which is abruptly released upon unlocking the means for storing potential energy solely acts on the hollow cylinder and not on the fluid reservoir. This may be particularly advantageous in cases in which the fluid reservoir in its initial (fully filled state) at the beginning of its usage has a relatively large mass which decreases overuse. A higher acceleration of the hollow cylinder would translate into a higher pressure in the pumping chamber. For the avoidance of doubt, all other options and preferences described herein-above and below with respect to other device features are applicable to both of these alternatives, i.e., regardless of whether the fluid reservoir is firmly attached to the hollow cylinder or not. In one embodiment, the fluid reservoir may be designed to be collapsible, such as by means of a flexible or elastic wall. The effect of such design is that upon repeated use of the device which involves progressive emptying of the reservoir, the flexible or elastic wall buckles or folds such as to reduce the internal volume of the reservoir, so that the negative pressure which is necessary for extraction of a certain amount of liquid is not required to increase substantially over the period of use. In particular, the reservoir may be designed as a collapsible bag. The advantage of a collapsible bag is that the pressure inside the reservoir is almost independent of the filling level, and the influence of thermal expansion is almost negligible. Also, the construction of such a reservoir type is rather simple and already well established. A similar effect can be achieved with a rigid container which has a moveable bottom (or wall) by means of which the interior volume of the reservoir can also be successively reduced. The container may be pre-installed in the device or may be needed to me inserted into the device. In some embodiments the container is removeable, in some embodiments the container is non-removeable after insertion. In a further aspect the invention relates to a kit comprising: a) a liquid pharmaceutical composition as defined above; and b) an inhalation device. Preferably, the inhalation device is an inhalation device as described above. The invention further relates to the following numbered items: 1. A liquid pharmaceutical composition comprising: a) at least one long-acting muscarinic receptor antagonist (LAMA) selected from the group consisting of glycopyrronium bromide, ipratropium bromide, umiclidium bromide, and revefenacin; b) at least one long-acting adrenoceptor agonist (LABA) selected from the group consisting of formoterol fumarate, salmeterol xinofoate; alformoterol tartarate, and vilanterol trifenate; and c) at least one inhaled corticosteroid (ICS) selected from the group consisting of beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, and fluticasone propionate; and wherein the composition is in the form of a solution for aerosolization. 2. The pharmaceutical composition according to item 1, wherein the liquid pharmaceutical composition additionally comprises ethanol. 3. The pharmaceutical composition according to item 1 or 2, wherein the liquid pharmaceutical composition comprises the at least one long acting muscarinic receptor antagonist in a concentration of up to about 30 mg / mL, or of from about 0.1 mg / mL to about 10 mg / mL or of from about 0.5 mg / mL to about 1.5 mg / mL, for example of about 1.0 mg / mL (based on the volume of the final pharmaceutical composition). 4. The pharmaceutical composition according to any one of the preceding items, wherein the at least one long-acting muscarinic receptor antagonist is glycopyrronium bromide. 5. The pharmaceutical composition according to any one of the preceding items, wherein the liquid pharmaceutical composition comprises the at least one long acting adrenoceptor agonist in a concentration of up to about 30 mg / mL, or of from about 0.05 mg / mL to about 10 mg / mL or of from about 0.1 mg / mL to about 1.0 mg / mL, for example of about 0.45 mg / mL. 6. The pharmaceutical composition according to any one of the preceding items, wherein the at least one long acting adrenoceptor agonist is formoterol fumarate. 7. The pharmaceutical composition according to any one of the preceding items, wherein the liquid pharmaceutical composition comprises the at least one inhaled corticosteroid in a concentration of up to about 30 mg / mL, or of from about 1.0 mg / mL to about 20 mg / mL or of from about 5 mg / mL to about 15 mg / mL. 8. The pharmaceutical composition according to any one of the preceding items, wherein the at least one inhalable corticosteroid is beclomethasone dipropionate and / or budesonide. 9. The pharmaceutical composition according to any one of the preceding items, wherein the at least one inhalable corticosteroid is beclomethasone dipropionate, preferably at a concentration of from about 5 mg / mL to about 10 mg / mL, for example of about 7.7 mg / mL to about 8.0 mg / mL. 10. The pharmaceutical composition according to any one of the preceding items, wherein the at least one inhalable corticosteroid is budesonide, preferably at a concentration of from about 10 mg / mL to about 20 mg / mL, or from about 12.5 mg / mL to about 17.5 mg / mL, for example of about 14.3 mg / mL mg / mL to about 14.6 mg / mL. 11. The pharmaceutical composition according to any one of the preceding items, wherein the pharmaceutical composition optionally comprises one or more pharmaceutically acceptable excipients. 12. The pharmaceutical composition according to any one of the preceding items, wherein the pharmaceutical composition is essentially free of a propellant. 13. The pharmaceutical composition according to any one of items 1 to 12 for use in the treatment or prevention of a respiratory disease or condition in a subject. 14. The pharmaceutical composition for use according to item 13, wherein the respiratory disease or condition is a pulmonary disease or condition. 15. The pharmaceutical composition for use according to item 13 or 14, wherein the respiratory disease is selected from asthma, and chronic obstructive pulmonary disease (COPD). 16. The pharmaceutical composition for use according to any one of items 13 to 15, wherein the pharmaceutical composition is aerosolized (and administered to a patient in need thereof) using an inhalation device. 17. The pharmaceutical composition for use according to item 16, wherein the inhalation device comprises a mechanical pumping unit adapted to pressurize and convey the liquid pharmaceutical composition. 18. The pharmaceutical composition for use according to item 17, wherein the mechanical pumping unit comprises a pressure cylinder and a piston reciprocally movable within the pressure cylinder. 19. The pharmaceutical composition for use according to item 18, wherein the piston is a hollow piston comprising a liquid channel through which the liquid pharmaceutical composition is conveyed. 20. The pharmaceutical composition for use according to item 18 or 19, wherein the piston is adapted to be in a fixed position and the pressure cylinder is adapted to be movable during operation of the pumping unit. 21. The pharmaceutical composition for use according to any one of items 16 to 20, wherein the inhalation device comprises at least one nozzle adapted to aerosolize the liquid pharmaceutical composition. 22. The pharmaceutical composition for use according to item 21, wherein the nozzle is an impingement-type nozzle comprising at least two ejection channels through which at least two streams of the liquid pharmaceutical composition are ejected. 23. The pharmaceutical composition for use according to item 22, wherein the at least two ejection channels are adapted to generate the at least two streams of the liquid pharmaceutical composition such that at least two of the at least two liquid streams collide in a collision point thereby aerosolizing the liquid pharmaceutical composition. 24. The pharmaceutical composition for use according to any one of items 17 to 23, wherein the pumping unit is adapted to pressurize the liquid pharmaceutical composition to pressure of at least 50 bar, specifically to a pressure within the range of from about 100 to about 250 bar. 25. The pharmaceutical composition according to any one of items 16 to 24, wherein the inhalation device is provided in a form of a portable, hand-held inhalation device (adapted to be operated by one or two hands of a user). 26. The pharmaceutical composition for use according to item 25, wherein the hand-held inhalation device comprises: (a) a housing (1) having a user-facing side; (b) an impingement-type nozzle (6) for generating the nebulised aerosol by collision of at least two liquid jets, the nozzle (6) being firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); (c) a fluid reservoir (2) arranged within the housing (1); and (d) a pumping unit arranged within the housing (1), the pumping unit having - an upstream end that is fluidically connected to the fluid reservoir (2); - a downstream end that is fluidically connected to the nozzle (6); wherein the pumping unit is adapted for pumping fluid (F) from the fluid reservoir (2) to the nozzle (6); wherein the pumping unit further comprises (i) a riser pipe (5) having an upstream end, wherein the riser pipe (5) is - adapted to function as a piston in the pumping unit, and - firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); and (ii) a hollow cylinder (9) located upstream of the riser pipe (5), wherein the upstream end of the riser pipe (5) is inserted in the cylinder (9) such that the cylinder (9) is longitudinally movable on the riser pipe (5); (iii) a lockable means for storing potential energy (7) when locked and for releasing the stored energy when unlocked, the means (7) being arranged outside of, and mechanically coupled to, the cylinder (9) such that unlocking the means (7) results in a propulsive longitudinal movement of the cylinder (9) towards the downstream end of the pumping unit. 27. The pharmaceutical composition for use according to any one of items 16 to 26, wherein the inhalation device is adapted to aerosolize the liquid pharmaceutical composition to form an aerosol comprising liquid droplets. 28. The pharmaceutical composition for use according to item 27, wherein the inhalation device is adapted to aerosolize the liquid pharmaceutical composition to form an aerosol with an average medium droplet size by volume (Dv50) of below 2.5 µm, specifically by a Dv50 of below 2.3 µm. 29. The pharmaceutical composition for use according to any one of items 16-28, wherein, during administration, the liquid pharmaceutical composition is in the form of an aerosol with an average medium droplet size by volume (Dv50) of below 2.5 µm; optionally below 2.3 µm. 30. The pharmaceutical composition for use according to any one of items 16 to 29, wherein the inhalation device is adapted to generate discrete doses of the aerosolized liquid pharmaceutical composition. 31. The pharmaceutical composition for use according to item 30, wherein one discrete dose of the aerosolized liquid pharmaceutical composition comprises from about 9 mg to about 13 mg, or from about 10.5 mg to about 11.5 mg of the aerosolized liquid pharmaceutical composition. 32. The pharmaceutical composition for use according to item 30 or 31, wherein the pharmaceutical composition comprises beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide and wherein one discrete dose of the aerosolized liquid pharmaceutical composition comprises beclomethasone dipropionate in an amount of from about 85 µg to about 90 µg, specifically of about 87 µg, formoterol fumarate in an amount of from about 4 µg to about 6 µg, specifically of about 5 µg and glycopyrronium bromide in an amount of from about 8 µg to about 10 µg, specifically of about 9 µg. 33. The pharmaceutical composition for use according to item 30 or 31 , wherein the pharmaceutical composition comprises budesonide, formoterol fumarate and glycopyrronium bromide and wherein one discrete dose of the aerosolized liquid pharmaceutical composition comprises budesonide in an amount of from about 150 µg to about 170 µg, specifically of about 160 µg, formoterol fumarate in an amount of from about 4 µg to about 6 µg, specifically of about 4.8 µg and glycopyrronium bromide in an amount of from about 10 µg to about 12 µg, specifically of about 11 µg. 34. A kit comprising: a) a liquid pharmaceutical composition according to any one of items 1 to 12; and b) an inhalation device. 35. The kit according to item 34, wherein the inhalation device comprises a mechanical pumping unit adapted to pressurize and convey the liquid pharmaceutical composition. 36. The kit according to item 35, wherein the mechanical pumping unit comprises a pressure cylinder and a piston reciprocally movable within the pressure cylinder. 37. The kit according to item 36, wherein the piston is a hollow piston comprising a liquid channel through which the liquid pharmaceutical composition is conveyed. 38. The kit according to item 35 or 37, wherein the piston is adapted to be in a fixed position and the pressure cylinder is adapted to be movable during operation of the pumping unit. 39. The kit according to any one of items 35 to 38, wherein the inhalation device comprises at least one nozzle adapted to aerosolize the liquid pharmaceutical composition. 40. The kit according to item 39, wherein the nozzle is an impingement-type nozzle comprising at least two ejection channels through which at least two streams of the liquid pharmaceutical composition are ejected. 41. The kit according to item 40, wherein the at least two ejection channels are adapted to generate the at least two streams of the liquid pharmaceutical composition such that at least two of the at least two liquid streams collide in a collision point thereby aerosolizing the liquid pharmaceutical composition. 42. The kit according to any one of items 35 to 41, wherein the pumping unit is adapted to pressurize the liquid pharmaceutical composition to pressure of at least 50 bar, specifically to a pressure within the range of from about 100 to about 250 bar. 43. The kit according to any one of items 35 to 42, wherein the inhalation device is provided in a form of a portable, hand-held inhalation device (adapted to be operated by one or two hands of a user). 44. The kit according to item 43, wherein the hand-held inhalation device comprises: (a) a housing (1) having a user-facing side; (b) an impingement-type nozzle (6) for generating the nebulised aerosol by collision of at least two liquid jets, the nozzle (6) being firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); (c) a fluid reservoir (2) arranged within the housing (1); and (d) a pumping unit arranged within the housing (1), the pumping unit having - an upstream end that is fluidically connected to the fluid reservoir (2); - a downstream end that is fluidically connected to the nozzle (6); wherein the pumping unit is adapted for pumping fluid (F) from the fluid reservoir (2) to the nozzle (6); wherein the pumping unit further comprises (i) a riser pipe (5) having an upstream end, wherein the riser pipe (5) is - adapted to function as a piston in the pumping unit, and - firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); and (ii) a hollow cylinder (9) located upstream of the riser pipe (5), wherein the upstream end of the riser pipe (5) is inserted in the cylinder (9) such that the cylinder (9) is longitudinally movable on the riser pipe (5); (iii) a lockable means for storing potential energy (7) when locked and for releasing the stored energy when unlocked, the means (7) being arranged outside of, and mechanically coupled to, the cylinder (9) such that unlocking the means (7) results in a propulsive longitudinal movement of the cylinder (9) towards the downstream end of the pumping unit. 45. The kit according to any one of items 35 to 44, wherein the liquid pharmaceutical composition is provided in a cartridge which is pre-installed in the inhalation device, or which may be inserted into the inhalation device. The following examples serve to illustrate the invention, however, should not be understood as restricting the scope of the invention. EXAMPLESExample 1Spray Tests and Droplet size distributions of inhalable compositionsA solutions comprising 8.04 mg / mL beclomethasone dipropionate, 0.46 mg / mL formoterol fumarate dihydrate and 1.02 mg / mL glycopyrronium bromide in ethanol was prepared. The solution has been tested for their suitability for administration using a soft mist inhaler. It was shown that the solutions were suitable for administration in nebulized form using a soft- mist inhaler with a working pressure of at least 200 bar and a spray duration between 1 and 2 sec (seconds). A repeated sprayability test with sufficient fine particle distribution as showed no clogging or blocking events of the device. Tables 1 shows the fractions of particle (droplet) sizes when the above-described solution was nebulized with a soft-mist inhaler. Droplet size was measured by laser diffraction. The term ^Event duration^ as used in Table 1 means the duration of the entire nebulization process in seconds (^Stdev^ means standard deviation). ^Dv10^ means that 10% of the overall number of particles has a mean diameter of the given value. Likewise, ^Dv50^ and ^Dv90^ means that 50% or 90%, respectively, of the overall number of particles has a mean diameter of the given value.Table 1: Spray test resultsAverage Stdev N SpraysEvent duration / s 1.68 0.03 6Transmission / % 89.01 0.58 6Dv10 / m 1.28 0.03 6Dv50 / m 2.24 0.04 6Dv90 / m 3.96 0.20 6The average droplet size distribution is depicted in Figure 7.Example 2Pharmaceutical Assessment of inhalable compositionsA BFG (beclometasone dipropionate, formoterol and glycopyrronium) inhalation solution was prepared for pharmaceutical assessment in a soft mist inhaler. The clear colourless solution inhalation solution was prepared by dissolving the three active substances in 25 mL ethanol solution to achieve the concentrations and target delivered dose shown in Table 2, under conditions of 30% relative humidity and 21°C.Table 2: Composition of Inhalation SolutionConcentrationDelivered DoseActive Substance(mg / mL) (mcg) Beclomethasone 8.04 88.88 dipropionate Formoterol fumarate 0.46 5.05 dihydrate Glycopyrronium 1.02 11.25 bromide The inhalation solution was loaded into four ethanol cartridges and two standard, semi- permeable cartridges. The cartridges were assembled into a Test Device soft mist inhaler (SOFTHALER), as disclosed in WO 2018 / 197730 A1 (15 mcL metered volume and no check valve), and into the reference device, RESPIMAT in the quantities below. ^ Test Device and ethanol cartridge: 2 units. ^ Test Device and standard cartridge: 1 unit. ^ RESPIMAT Device and ethanol cartridge: 2 units. ^ RESPIMAT Device and standard cartridge: 1 unit. Spray characteristics were assessed on each configuration by evaluating the droplet size distribution (DSD) of the delivered dose by each device as measured by laser diffraction using a MALVERN SPRAYTEC (MALVERN PANALYTICAL) with a 100% humidification system incorporated to mimic the conditions human respiratory tract. The MALVERN SPRAYTEC was fitted with a 300 mm lens, and the inhalation cell was fitted vertically with a USP throat at the inlet and a filter (sealed with parafilm if necessary) at the outlet. A USP throat, also known as a United States Pharmacopeia (USP) induction port (IP), is intended to provide a common standard to compare different formulations of an inhaler. The system was placed under vacuum, to generate an air flow of 28.3 L / min, which was verified at the throat inlet and checked until the air flow rate was maintained and stable. The following SPRAYTEC parameters were loaded, as shown in Table 3 below:Table 3: MALVERN SPRAYTEC ParametersSPRAYTEC ParametersInhalation cell with Induction port / USP Hardware throat Measurement Type Rapid Acquisition Rate 2.5 kHz Lens Standard 300 mm Angle Vertical Background Measurement Duration 10 secs Background Alarms Default Events Number 1 Event Duration / Measurement time 2 secs Data Collection Start 50.0 ms before the trigger Trigger Type Transmission drops to level 95 % Purge Airflows enabled (Transmitter and No Detector) Flow Rate 28.3 L / min Particle: Water RI (Real): 1.33 RI (Imaginary): 0.00 Optical Properties Density of Particle: 1.00 Dispersant: Air RI: 1.00 Multiple Scattering Enabled Average Dv10, Dv50, Dv90, SPAN, % Parameters Measured <10 m, % <5 mPrior to the analysis, the inhalation devices were primed, and the inhaler mouthpieces were cleaned, including the metal part inside the mouthpiece with a clean, dry swab or tissue. Consistent results were obtained for all configurations of device and cartridge, and the assessment demonstrated that a fully formed spray was generated for multiple actuations through the Test device as intended. Twelve sprays were analysed in total. Table 4 presents the DSD results for the Test Device and ethanol cartridge and Figure 8 shows the DSD profile.Table 4: DSD Results for PoP BFG formulation tested in the Test Device with ethanolcartridge Parameter Average Result Standard DeviationEvent duration 1.62 0.13 (seconds) D10 ( m) 1.26 0.05D50 ( m) 2.22 0.18D90 ( m) 3.97 0.51GSD ( m) 2.36 0.38Span 1.21 0.12 Volume < 5 m (%) 96.45 2.81 Volume < 10 mcm (%) 99.91 0.27 D90represents the droplet size below which 90% of the total volume of droplets is contained. It is a common parameter used to characterize droplet size distributions, alongside other values like D10(below which 10% of the volume is contained) and D50(the median, or 50% point). D50, or the median droplet diameter, represents the droplet size below which 50% of the total droplet volume is contained, and is a common way to characterize droplet size distributions, providing a single value that summarizes the overall size of droplets. D10represents the droplet diameter below which 10% of the total droplet volume is found, essentially a percentile of the cumulative volume distribution, and is a measure used in spray and aerosol technology to characterize the smallest droplets within a sample. The DSD was determined by calculating the width of the droplet size distribution, which is a dimensionless number also known as ^Span.^ Span is determined according to the following formula: Span = (D90 D10) / D50, where D10, D50, and D90 represents the cumulative particle size distribution of 10%, 50%, and 90% particles, respectively, as described above. All DSD parameter data from the Test Device were considered comparable or better than the DSD parameter data generated from the RESPIMAT reference product. Furthermore, two feasibility studies were conducted. Figure 9 presents the delivered dose and fine particle fraction (calculated as the fine particle dose expressed as percent of delivered dose) determined for Test Device in comparison with the reference pressurised metered dose inhaler (pMDI B / N: 1140705). Figure 10 shows the measures shot weight values for the Test Device when tested periodically over two days. The fine particle fraction for the Test Device was demonstrated to be more than double that of the reference pressurised metered dose inhaler. During the feasibility assessment, at least one Test Device had a loss of prime when left overnight, as shown by shot 4 in Figure 10. This issue was attributed to the design of that version of the device, and was resolved with the introduction of a check valve system. The above noted studies have demonstrated that the Test Device fine particle fraction was significantly greater than the Reference Products, indicating a greater fraction of the Test Device delivered dose would reach the lung. This indicates that a lower delivered dose is required for the Test Device to achieve an equivalent therapeutic dose (lung dose) to the Reference Products.

Claims

Claims 1. A liquid pharmaceutical composition comprising: a) at least one long-acting muscarinic receptor antagonist (LAMA) selected from the group consisting of glycopyrronium bromide, ipratropium bromide, umiclidium bromide, and revefenacin; b) at least one long-acting adrenoceptor agonist (LABA) selected from the group consisting of formoterol fumarate, salmeterol xinofoate; alformoterol tartrate, and vilanterol trifenate; and c) at least one inhaled corticosteroid (ICS) selected from the group consisting of beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, and fluticasone propionate; and wherein the composition is in the form of a solution for aerosolization.

2. The pharmaceutical composition according to claim 1, wherein the liquid pharmaceutical composition additionally comprises ethanol.

3. The pharmaceutical composition according to claim 1 or 2, wherein the at least one long-acting muscarinic receptor antagonist is glycopyrronium bromide; and / or wherein the at least one long acting adrenoceptor agonist is formoterol fumarate; and / or wherein the at least one inhalable corticosteroid is beclomethasone dipropionate and / or budesonide.

4. The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition optionally comprises one or more pharmaceutically acceptable excipients.

5. The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition is essentially free of a propellant.

6. The pharmaceutical composition according to any one of claims 1 to 5 for use in the treatment or prevention of a respiratory disease or condition in a subject, wherein the respiratory disease or condition is a pulmonary disease or condition; optionally wherein the respiratory disease is selected from asthma, and chronic obstructive pulmonary disease (COPD).

7. The pharmaceutical composition for use according to claim 6, wherein the pharmaceutical composition is aerosolized using an inhalation device.

8. The pharmaceutical composition for use according to any one of claims 6 or 7, wherein the inhalation device is provided in a form of a portable, hand-held inhalation device adapted to be operated by one or two hands of a user.

9. The pharmaceutical composition for use according to any one of claims 7 to 8, wherein the inhalation device is a soft-mist inhaler.

10. The pharmaceutical composition for use according to any one of claims 7 to 9, wherein the inhalation device comprises a mechanical pumping unit comprising a pressure cylinder and a piston reciprocally movable within the pressure cylinder, and wherein the piston is adapted to be in a fixed position and the pressure cylinder is adapted to be movable during operation of the pumping unit.

11. The pharmaceutical composition for use according to any one of claims 8 to 10, wherein the hand-held inhalation device comprises: (a) a housing (1) having a user-facing side; (b) an impingement-type nozzle (6) for generating the nebulised aerosol by collision of at least two liquid jets, the nozzle (6) being firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); (c) a fluid reservoir (2) arranged within the housing (1); and (d) a pumping unit arranged within the housing (1), the pumping unit having - an upstream end that is fluidically connected to the fluid reservoir (2); - a downstream end that is fluidically connected to the nozzle (6); wherein the pumping unit is adapted for pumping fluid (F) from the fluid reservoir (2) to the nozzle (6); wherein the pumping unit further comprises (i) a riser pipe (5) having an upstream end, wherein the riser pipe (5) is - adapted to function as a piston in the pumping unit, and - firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); and(ii) a hollow cylinder (9) located upstream of the riser pipe (5), wherein the upstream end of the riser pipe (5) is inserted in the cylinder (9) such that the cylinder (9) is longitudinally movable on the riser pipe (5); (iii) a lockable means for storing potential energy (7) when locked and for releasing the stored energy when unlocked, the means (7) being arranged outside of, and mechanically coupled to, the cylinder (9) such that unlocking the means (7) results in a propulsive longitudinal movement of the cylinder (9) towards the downstream end of the pumping unit.

12. The pharmaceutical composition for use according to claim 11, wherein the inhalation device is adapted to aerosolize the liquid pharmaceutical composition to form an aerosol with an average medium droplet size by volume (Dv50) of below 2.5 µm, specifically by a Dv50 of below 2.3 µm.

13. The pharmaceutical composition for use according to any one of claims 7-12, wherein, during administration, the liquid pharmaceutical composition is in the form of an aerosol with an average medium droplet size by volume (Dv50) of below 2.5 µm; optionally below 2.3 µm.

14. The pharmaceutical composition for use according to any one of claims 6 to 13, wherein the pharmaceutical composition comprises beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide and wherein one discrete dose of the aerosolized liquid pharmaceutical composition comprises beclomethasone dipropionate in an amount of from about 85 µg to about 90 µg, specifically of about 87 µg, formoterol fumarate in an amount of from about 4 µg to about 6 µg, specifically of about 5 µg and glycopyrronium bromide in an amount of from about 8 µg to about 10 µg, specifically of about 9 µg.

15. The pharmaceutical composition for use according to any one of claims 6 to 13, wherein the pharmaceutical composition comprises budesonide, formoterol fumarate and glycopyrronium bromide and wherein one discrete dose of the aerosolized liquid pharmaceutical composition comprises budesonide in an amount of from about 150 µg to about 170 µg, specifically of about 160 µg, formoterol fumarate in an amount of from about 4 µg to about 6 µg, specifically of about 4.8 µg and glycopyrronium bromide in an amount of from about 10 µg to about 12 µg, specifically of about 11 µg.

16. A kit comprising: a) a liquid pharmaceutical composition according to any one of items 1 to 5; and b) a hand-held inhalation device.

17. The kit according to claim 16, wherein the hand-held inhalation device comprises:(a) a housing (1) having a user-facing side; (b) an impingement-type nozzle (6) for generating the nebulised aerosol by collision of at least two liquid jets, the nozzle (6) being firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); (c) a fluid reservoir (2) arranged within the housing (1); and (d) a pumping unit arranged within the housing (1), the pumping unit having - an upstream end that is fluidically connected to the fluid reservoir (2); - a downstream end that is fluidically connected to the nozzle (6); wherein the pumping unit is adapted for pumping fluid (F) from the fluid reservoir (2) to the nozzle (6); wherein the pumping unit further comprises (i) a riser pipe (5) having an upstream end, wherein the riser pipe (5) is - adapted to function as a piston in the pumping unit, and - firmly affixed to the user-facing side of the housing (1) such as to be immobile relative to the housing (1); and (ii) a hollow cylinder (9) located upstream of the riser pipe (5), wherein the upstream end of the riser pipe (5) is inserted in the cylinder (9) such that the cylinder (9) is longitudinally movable on the riser pipe (5); (iii) a lockable means for storing potential energy (7) when locked and for releasing the stored energy when unlocked, the means (7) being arranged outside of, and mechanically coupled to, the cylinder (9) such that unlocking the means (7) results in a propulsive longitudinal movement of the cylinder (9) towards the downstream end of the pumping unit.

18. The kit according to claim 16 or 17, wherein the liquid pharmaceutical composition is provided in a cartridge which is pre-installed in the inhalation device or which may be inserted into the inhalation device.

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