Please select the eligibility criteria that correspond to the clinical trial below.
Title: Positive Expiratory Pressure for the Treatment of Acute Asthma Exacerbations in Children: A Randomized Controlled Trial
Brief Summary: Asthma is a leading cause of emergency department (ED) visits for children. A novel way of treating asthma is the use of positive expiratory pressure (PEP). Positive expiratory pressure works by creating pressure in the lungs to keep airways open and to clear mucus from the lungs. PEP is already used in the treatment of asthma at the investigators institution, but studies evaluating the efficacy of PEP therapy in asthma exacerbations do not exist. This study plans to learn more about the use of PEP therapy in the treatment of asthma exacerbations in children in the emergency department. Specifically, the study aims to evaluate if PEP therapy reduces the severity of asthma exacerbations in children and if it reduces the need for additional therapies and admission to the hospital. This study will be a randomized control trial comparing children who receive standard therapy to those who receive standard therapy plus PEP therapy in the treatment of asthma exacerbations. Children age 2 to 18 years presenting to the ED with moderate to severe asthma exacerbations will be included in the study. Reduction in clinical asthma severity will be measured by change in the Pulmonary Asthma Score (the respiratory severity score used at the investigators institution). The need for additional therapies and hospitalization will also be evaluated.


Options:
A: Inclusion Criteria:

* Adult Patients With Acute Asthma Attacks

Exclusion Criteria:

* Patient Has Any Known Or Suspected, Acute Or Chronic Cause For Their Pulmonary Symptoms Other Than Asthma (E.G., Copd, Chronic Heart Failure, Etc.)
* Patient Has A Smoking History (20 Cigarettes Per Day) Of More Than 15 Years
* Patient Has A Disease Of The Cardiovascular, Hepatic, Renal, Hematologic Systems, Or Other Severe Disease
B: Inclusion Criteria:

* reversibility of bronchial obstruction after administration of bronchodilator drugs for at least 10% in FEV1
* a clinical diagnosis of acute severe asthma
* a history of asthma over 1 year
* duration of the crisis of current asthma lasting less than seven days

Exclusion Criteria:

* were unable to understand or perform the spirometric maneuver
* smoking (within the last 3 years associated with a higher consumption of 100 cigarettes/year)
* other pulmonary comorbidities
* lower to upper airways
* heart failure
* heart rate greater than 150 bpm
* systolic pressure below 90 mmHg or greater than 150 MHG
* pregnancy
* inability to stay inline with the trunk forward
C: Inclusion Criteria:

* Subjects meeting all of the following criteria will be considered for admission to the study:

  1. Male or female 18 to 65 years of age, inclusive;
  2. Self-reported history of physician-diagnosed and treated asthma for ≥ 3 months prior to randomization;
  3. A diagnosis of an acute exacerbation of asthma upon presentation at the ED as defined by dyspnea and evidence of bronchospasm;
  4. Received the following Standardized Treatment within a 2-hour time window and prior to obtaining the Qualifying Spirometry value(FEV1):

     * Supplemental oxygen given to maintain oxygen saturation as measured by pulse oximetry of ≥ 90% as needed;
     * Albuterol 5-15mg of albuterol via nebulizer prior to the qualifying spirometry evaluation; simultaneously with
     * Ipratropium 0.5-1.5 mg of ipratropium via nebulizer prior to the qualifying spirometry evaluation;
     * One dose of corticosteroid of at least 50 mg given orally (prednisone) or intravenously (methylprednisolone) or the equivalent dose of another corticosteroid.
  5. FEV1 of ≤ 50% of predicted; NOTE: Spirometry to measure the subject's FEV1 expressed as % of predicted within 30 minutes of completing administration of 5 mg (but not more than 15 mg) albuterol and 0.5 mg (but not more than 1.5 mg) of ipratropium..
  6. Negative urine pregnancy test for all females of child-bearing potential;
  7. ECG with no dysrhythmias (except sinus tachycardia);
  8. No clinical or electrocardiographic signs of ischemic heart disease as determined by the Investigator; and
  9. Legally effective written informed consent obtained prior to starting any mandated study procedures

Exclusion Criteria:

Subjects will be excluded if they meet any of the following criteria:

1. Administration of a parenteral (intravenous or subcutaneous) beta agonist (e. g., albuterol, terbutaline, epinephrine) within 6 hours prior to randomization;
2. A current or prior diagnosis or suspected diagnosis of COPD or other chronic lung disease other than asthma;
3. Presence of pneumonia;
4. Presence of significant other respiratory dysfunction such as pneumothorax, pneumomediastinum, or pulmonary edema;
5. Known or suspected vocal cord dysfunction syndrome;
6. Presence of aspirated foreign body (known or suspected);
7. History or any current clinical evidence suggesting cardiomyopathy or congestive heart failure;
8. History or presence of tachyarrhythmias, with the exception of sinus tachycardia;
9. Heart rate ≥ 140 bpm;
10. Hypokalemia, defined as subjects with serum potassium level of \<2.8 mEq/L (≤2.8 mmol/L) obtained at Screening (local stat lab, blood gas analysis, or other point of care device) with the following exception:

    For the subjects using non-potassium-sparing diuretics (i.e. loop-diuretic or thiazide diuretic) without "potassium-sparing diuretics" (e.g., Triamterene or Spironolactone) OR without potassium supplementation of at least KCl 20 mEq/day whose potassium level \<3.5 mEq/L (\<3.5 mmol/L) at Screening.
11. Significant cardiac, renal, hepatic, endocrine, metabolic, neurologic or other systemic disease. A significant disease will be defined as one which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study or the subject's ability to participate in the trial;
12. Self-reported history of greater than 20 pack-yr smoking history;
13. Fever ≥ 102.0 ºF (38.9 ºC);
14. Uncontrolled hypertension defined as a blood pressure ≥ 170/100 mm Hg (22.7/13.3 kPa);
15. Need for immediate intubation, mechanical ventilation, or non-invasive positive pressure ventilation as determined by the Investigator;
16. Pregnant or lactating females;
17. Participated in another clinical study with an investigational drug within 30 days of randomization;
18. Positive urine drug screen for cocaine, methamphetamine or PCP unless, in the Investigator's clinical judgment, a single positive result is explained by exposure to a non-illicit drug product (i.e., is a false positive). For example, phenylpropanolamine or methylphenidate may read positive in a methamphetamine screen; dextromethorphan in a PCP screen.
19. Any subject with a known allergy to components of the MN-221 drug product;
20. Any subject with a known allergy to other beta agonists;
21. Previous exposure to MN-221; or
22. Use of theophylline, beta blockers, digoxin, MAO inhibitors, or tricyclic antidepressants within 2 weeks prior to randomization.

Use of non-potassium-sparing diuretics (i.e. Thiazide or Loop-diuretic) without potassium-sparing diuretic OR without potassium supplementation \>20 mEq/day within 2 weeks prior to randomization and if serum potassium level at Screening \<3.5 mEq/L (\<3.5 mmol/L).
D: Inclusion Criteria:

* Age \>= 2 and \< 18 years of age
* Established diagnosis of asthma, defined as at least two prior episodes of treatment with bronchodilators in their lifetime
* Initial ED presentation with a moderate to severe asthma exacerbation, as defined by a pulmonary asthma score (PAS) \>7
* PAS score \>7 and \<12 after completion of first line therapies (three doses albuterol/ipratropium bromide and oral corticosteroids)

Exclusion Criteria:

* Do not receive complete first line therapies
* Immediately receive a disposition (admission or discharge) as determined by the treating clinician after completion of first line therapies
* Receive prednisone or more than two doses of inhaled bronchodilators prior to main ED evaluation (e.g. during EMS transport or primary care visit)
* Co-morbid illnesses interfering with or contraindicated to usual asthma therapy (e.g. facial or airway abnormalities, pneumonia, chronic lung disease, congenital heart disease, cystic fibrosis, or pneumothorax)
* Critically ill at presentation
* Pregnant women (women known to be pregnant at the time of enrollment)

Answer: D