Provided is a system (10) for determining a probability of a CORD exacerbation in a subject. The system comprises a first inhaler (100) for delivering a rescue medicament to the subject. The rescue medicament may be suitable for treating the subject's acute respiratory disease, for example by effecting rapid dilation of the bronchi and bronchioles upon inhalation of the medicament. The first inhaler has a use-detection system (12B) configured to determine a rescue inhalation performed by the subject using the first inhaler. The system optionally includes a second inhaler for delivering a maintenance medicament to the subject during a routine inhalation A sensor system (12A) is configured to measure a parameter relating to airflow during the rescue inhalation and/or during the routine inhalation, when the second inhaler is included in the system. The system further comprises a processor (14) configured to determine a number of the rescue inhalations during a first time period, and receive the parameter measured for at least some of the rescue and/or routine inhalations. The processor then determines, using a weighted model, the probability of the CORD exacerbation based on the number of rescue inhalations and the parameters. The model is weighted such that the parameters are more significant in the probability determination than the number of rescue inhalations. Further provided is a method for determining the probability of a COPD exacerbation in a subject, which method employs the weighted model.

A pharmaceutical inhalation aerosol and a preparation method therefor. The preparation method comprises the following steps: (1) mixing glycopyrronium bromide coarse powder with indacaterol fine powder, or glycopyrronium bromide coarse powder with indacaterol coarse powder, or glycopyrronium bromide fine powder with indacaterol coarse powder in proportion to obtain a glycopyrronium bromide and indacaterol mixture; (2) micronizing, by a crushing device under pressure, the glycopyrronium bromide and indacaterol mixture prepared in step (1) to obtain a micronized glycopyrronium bromide and indacaterol mixture; and (3) adding the micronized glycopyrronium bromide and indacaterol mixture prepared in step (2) to an aluminum can, performing valve sealing, and filling with a propellant. In the glycopyrronium bromide/indacaterol compound inhalation aerosol prepared by the method, the effective deposition rate of glycopyrronium bromide is significantly improved, and the degree of co-deposition of glycopyrronium bromide and indacaterol is high. The prepared inhalation aerosol is convenient to carry and low in price, has higher medication compliance compared with an inhalation powder aerosol, and is more widely used than a nebulizer.

Pseudomonas aeruginosa (PA) leads to chronic respiratory infections especially in patients with cystic fibrosis patients and chronic obstructive pulmonary disease (COPD), characterized by a high morbidity. After screening Lactobacilli coming from CF expectoration, on their capacity to inhibit two Pseudomonas aeruginosa (PA) virulence factors (elastase, pyocyanin), the inventors evaluated the effect of intranasal administration of Lactobacilli on PA murine pneumonia. The primary outcome was the bacterial lung load 24 hours after PA induced pneumonia. To understand the role of Lactobacillus, the chemokines, the pro and anti-inflammatory BAL rates were also measured. The administration of Lactobacilli cocktail 18 h prior the PA lung infection decreases significantly the lung bacterial load at 24 h post-infection. Although the mechanisms need to be deeply explored, an immunomodulation effect may be involved, notably through the recruitment of neutrophils. Thus the present relates to a method of treating a Pseudomonas aeruginosa respiratory tract infection in a patient in need thereof comprising administering to the patient's respiratory tract a therapeutically effective amount of at least one Lactobacillus strain.

Provided herein are compounds, such as compounds of Formula I, that bind to androgen receptors and/or modulate activity of androgen receptors. Also provided are methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions. ##STR00001##

The present disclosure features disclosed method of treating disorders such as COPD, bronchitis and/or asthma using disclosed compounds, optionally together with one or more additional active agents. Contemplated methods include administrating orally or by inhalation to a patient one or more disclosed compounds.

The present disclosure features disclosed method of treating disorders such as COPD, bronchitis and/or asthma using disclosed compounds, optionally together with one or more additional active agents. Contemplated methods include administrating orally or by inhalation to a patient one or more disclosed compounds.

The present invention relates to compounds of formula I

##STR00001##

or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein
R.sub.1 is C.sub.1-C.sub.3alkyl optionally substituted with F, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3alkoxy;
X represents a bond or C.sub.1-C.sub.3alkylene optionally substituted with OH, ONO, ONO.sub.2;
R.sub.2 is H, OH, ONO, ONO.sub.2, C(O)OH, C(O)OC.sub.1-C.sub.3alkyl, CHO, CN, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)—C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl, CR.sub.8═N—OR.sub.9, CR.sub.8═N—NR.sub.10R.sub.11, CR.sub.8═NR.sub.12 or CR.sub.8═N—ONO.sub.2;
R.sub.3 is C.sub.1-C.sub.6alkyl optionally substituted with F, OH, ONO, ONO.sub.2, C.sub.1-C.sub.3alkoxy, C.sub.3-C.sub.6cycloalkyl; C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl; R.sub.4 is C.sub.1-C.sub.6alkyl optionally substituted with C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6alkoxy, F, ONO, ONO.sub.2; C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl;
R.sub.5 is H, SO.sub.2NR.sub.13R.sub.14, NHSO.sub.2NR.sub.13R.sub.14;
R.sub.6 is H or C.sub.1-C.sub.3alkyl;
R.sub.7 is H, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3alkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C.sub.1-C.sub.3alkyl, F;
R.sub.8 is H, CH.sub.3 or C.sub.2H.sub.5;
R.sub.9: H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)—C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl;
R.sub.10 and R.sub.11 are each independently H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)—C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is op

Compositions and methods for making and using stable, homogeneous budesonide compositions are disclosed.

Compositions and methods for making and using stable, homogeneous budesonide compositions are disclosed.

The present invention is related to a pharmaceutical composition for nebulization administration comprising an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and optionally a long-acting muscarinic antagonist (LAMA) to be used in the treatment of respiratory diseases, especially in asthma and chronic obstructive pulmonary disease (COPD), and process for the preparation 5 thereof. More particularly, the pharmaceutical compositions herein include beclometasone dipropionate (BPD), formoterol fumarate (FF) and optionally glycopyrronium bromide (GB). The invention also relates to the use of said pharmaceutical formulation in a soft mist inhaler.