Low-dose inhaled corticosteroids and the prevention of death from asthma

There are no specific recommendations about when to initiate corticosteroid treatment. Data suggest that oral steroids should be used in patients with stages II and III disease, with moderate to severe or progressive symptoms and chest radiograph changes. It is unclear if asymptomatic patients will ever need therapy, even if they have diffuse lung infiltration. Because there is no consensus on the optimal dosage or duration of therapy, the course is individualized for each patient. A recent joint statement of the American Thoracic Society, the European Respiratory Society, and the World Association of Sarcoidosis and Other Granulomatous Disorders 1 included the following guidelines: an initiation dose of prednisone of 20 to 40 mg per day or its equivalent is recommended. Every-otherday dosing may be considered. Patients should be evaluated after one to three months for response. Patients who fail treatment after three months usually will not respond to a more protracted course of treatment. In responders, the prednisone dosage should be tapered to 5 to 10 mg per day or to an every-otherday regimen, and therapy should continue for a minimum of 12 months. 1 There is no consensus guidance on treatment beyond two years. 2 Patients must be monitored after cessation of treatment for possible relapse; some patients will require long-term low-dose therapy to prevent recurrent disease. 1

In a small study in healthy volunteers, the slightly less potent CYP3A inhibitor ketoconazole increased the exposure of fluticasone propionate after a single inhalation by 150%. This resulted in a greater reduction of plasma cortisol as compared with fluticasone propionate alone. Co-treatment with other potent CYP3A inhibitors, such as itraconazole and cobicistat-containing products, and moderate CYP3A inhibitors, such as erythromycin, is also expected to increase the systemic fluticasone propionate exposure and the risk of systemic side effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

The most commonly reported side effects were: oral thrush , nausea , headache , and pain in the pharynx or larynx . More rarely reported side effects (occurring in <1% of patients during the clinical trial) include: tachycardia , palpitations , dry mouth , allergic reaction ( bronchospasm , dermatitis , hives ), pharyngitis , muscle spasms , tremor , dizziness , insomnia , nervousness , and hypertension . Patients experiencing an allergic reaction or increase in difficulty breathing while using this medication should immediately discontinue its use and contact their physician. [4]

Background and study aims
Acute respiratory distress syndrome (ARDS) is a disease in which the lungs are inflamed, wet and there is difficulty transmitting oxygen from the air that enters the lung as part of the breathing process into the blood. It has many causes including infectious and non-infectious. The objectives of this study were to add a gas called nitric oxide(NO) to the air that participants were breathing in order to raise the oxygen level in the blood in hopes of improving outcome in participants with ARDS.

Who can participate?
Patients aged 18 and over, regardless of sex, who have ARDS and are on a breathing machine (called a ventilator) in order to enable oxygen transfer into the blood.

What does the study involve?
The study compared inhaled nitric oxide (INO) added to the air the patient was breathing though the machine with a placebo nitrogen, a safe gas that makes up most of the air that we breathe and would have no effect on ARDS. All participants will receive the same treatment that they would have received for ARDS, even if they had not participated in the study. If patients were randomly allocated to the group receiving inhaled nitric oxide, this would have been the additional therapy.

What are the possible benefits and risks of participating?
By participating it is possible that the subject will have improved oxygenation and that this may lead to improved outcome. There are no anticipated potential side effects of the treatment when delivered at the doses that will be used in this study.

Where is the study run from?
There were 35 centers taking part in this trial and the lead center is St. Johns Mercy Hospital St. Louis, Missouri.

When is study starting and how long is it expected to run for?
The start date of the study was 1996 and the duration of the study was approximately 3 years. Recruitment of participants was until late summer/fall 1999.

Who is funding the study?
The study was funded by INO Therapeutics (Now called IKARIA). They paid the costs associated with the trial.

Who is the main contact?
Phil Dellinger
dellinger-phil@

Theophylline down-regulates inflammatory and immune cell function in vitro and in vivo in animals with airway inflammation [ 16,17 ]. In patients with allergic asthma, it attenuates the late phase increase in airway obstruction and airway responsiveness to histamine, decreases allergen-induced migration of activated eosinophils into the bronchial mucosa, and decreases the sputum eosinophil count [ 8,9,18 ]. Moreover, withdrawal of theophylline from patients with severe chronic asthma receiving high-doses of inhaled glucocorticoid therapy results in increased symptoms of asthma accompanied by an increase in the number of activated cytotoxic T-lymphocytes in the bronchial mucosa and an increase in helper T-lymphocytes in the airway epithelium [ 7 ]. The reduction in nocturnal worsening of lung function when theophylline is used is associated with both a decrease in the percentage of neutrophils and a decrease in stimulated leukotriene B4 from macrophages in early morning bronchoalveolar lavage fluid [ 19 ]. An in depth review of in vitro and in vivo studies demonstrating the immunomodulatory, anti-inflammatory, and glucocorticoid-sparing effects of theophylline has been published [ 20 ].

Low-dose inhaled corticosteroids and the prevention of death from asthma

low-dose inhaled corticosteroids and the prevention of death from asthma

Background and study aims
Acute respiratory distress syndrome (ARDS) is a disease in which the lungs are inflamed, wet and there is difficulty transmitting oxygen from the air that enters the lung as part of the breathing process into the blood. It has many causes including infectious and non-infectious. The objectives of this study were to add a gas called nitric oxide(NO) to the air that participants were breathing in order to raise the oxygen level in the blood in hopes of improving outcome in participants with ARDS.

Who can participate?
Patients aged 18 and over, regardless of sex, who have ARDS and are on a breathing machine (called a ventilator) in order to enable oxygen transfer into the blood.

What does the study involve?
The study compared inhaled nitric oxide (INO) added to the air the patient was breathing though the machine with a placebo nitrogen, a safe gas that makes up most of the air that we breathe and would have no effect on ARDS. All participants will receive the same treatment that they would have received for ARDS, even if they had not participated in the study. If patients were randomly allocated to the group receiving inhaled nitric oxide, this would have been the additional therapy.

What are the possible benefits and risks of participating?
By participating it is possible that the subject will have improved oxygenation and that this may lead to improved outcome. There are no anticipated potential side effects of the treatment when delivered at the doses that will be used in this study.

Where is the study run from?
There were 35 centers taking part in this trial and the lead center is St. Johns Mercy Hospital St. Louis, Missouri.

When is study starting and how long is it expected to run for?
The start date of the study was 1996 and the duration of the study was approximately 3 years. Recruitment of participants was until late summer/fall 1999.

Who is funding the study?
The study was funded by INO Therapeutics (Now called IKARIA). They paid the costs associated with the trial.

Who is the main contact?
Phil Dellinger
dellinger-phil@

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