Please select the eligibility criteria that correspond to the clinical trial below.
Title: Timing of Hypertonic Saline Inhalation Relative to Airways Clearance in Cystic Fibrosis
Brief Summary: Lung disease is the predominant cause of morbidity and mortality in Cystic Fibrosis (CF) with 80% of deaths resulting directly or indirectly from pulmonary disease. Abnormal airway clearance causes retention of mucus resulting in frequent chest infections. Physiotherapists use different techniques to help clear mucus from the lungs of patients with CF. Inhaled medications and airways clearance techniques (ACTs) are central to a CF patient's daily treatment and are often coordinated.

Burden of treatment is a common reason for non-adherence in this patient group, and streamlining of treatment timings is sought to optimize adherence whilst ensuring efficacy to an often complex daily regimen of inhaled bronchodilators, nebulizers and ACTs. A gap in the research exists as to the optimal timing of Hypertonic Saline (HTS) and ACT within the daily regimen. A study to show whether the timing of HTS around ACT is significant, can better inform patients and potentially allow more flexibility around their treatment regimen.

Lung Clearance Index (LCI) has shown good sensitivity to abnormalities in lung function compared with spirometry and has demonstrated a treatment effect in other trials. LCI may be a suitable tool therefore, to assess intervention strategies aimed at airways clearance in CF. This study aims to compare the effects ACTs after HTS inhalation versus ACTs during HTS inhalation as measured by LCI.

It is a randomized, crossover trial of ACTs after HTS inhalation compared with ACTs during HTS inhalation in adult CF patients during day 10-14 of a hospital admission for treatment of a pulmonary exacerbation. Patients will be randomized to receive 1 of the treatment session options on the first day and the reverse on the second day.

The primary objective of this study is to compare the change in LCI (a measure of lung function) at 90 minutes post treatment with ACTs after HTS inhalation compared with ACTs during HTS inhalation in adult CF patients.

LCI (lung clearance index) ACT (airway clearance technique) HTS (hypertonic saline)


Options:
A: Inclusion Criteria:

1. Male or female patients with a documented diagnosis of CF aged ≥18 years.
2. Written informed consent.
3. At least day 10 - 14 of IV antibiotic therapy during a hospital admission for a pulmonary exacerbation.
4. Patients must be able to perform acceptable spirometric manoeuvres, according to the American Thoracic Society/ERS (ATS/ERS) standards (Miller, Hankinson et. al. 2005).
5. Patient with an FEV1% predicted of ≥ 40%predicted (Stanojevic, Wade et al. 2008).
6. Patients who are productive of sputum from screening visit to study visit 1 (≥10g over 24 hours).
7. Patients who have been prescribed HTS (Nebusal 7%) and have successfully completed a challenge test.
8. Any other chronic medication must have commenced therapy 4 weeks prior to screening and be willing to continue this therapy for the entire duration of the study.

Exclusion Criteria:

1. Day 1-9 of IV antibiotic therapy during a hospital admission.
2. Patients who are colonized with Burkholderia cepacia complex.
3. Patient who are HTS naive.
4. Patients who have an intolerance to HTS.
5. Patients who are currently participating in another study or have participated in another study with an investigational drug within one month of screening.
6. Clinically significant disease or medical condition other than CF or CF-related conditions that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data.

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B: Inclusion Criteria:

* Male or female 6 years of age or older at enrollment and be competent in performing spirometry.
* Confirmed diagnosis of CF.
* FEV1\> 45% predicted as calculated by Wang reference equations
* Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
* Clinically stable at enrollment with no evidence of respiratory exacerbation within a month of enrollment as assessed by the site CF Physician.
* Willingness to adhere to prescribed treatment regimen.

Exclusion Criteria:

* Diagnosis of Allergic Broncho-Pulmonary Aspergillosis, or a persistent culture for B.cepacia complex within the previous 1 year period
* .On active treatment for non Tuberculous Mycobacterium.
* Use of intravenous antibiotics within the previous 14 days of enrollment.
* Initiation and or change in maintenance therapy within 14 days of enrollment.
* Use of systemic corticosteriods (1mg/kg if \< 20 kg or 20 mg of prednisone per day) within 14 days of enrollment.
* Concurrent participation in another study that could potentially affect the present study.
* Haemoptysis of over 20 mls on more than 2 occasions within the previous 30 days from enrollment.
* A pneumothorax in the six months preceding the study.
* Presence of a condition or abnormality that in the opinion of the site CF Physician would compromise the safety of the patient or the quality of the data.
C: Inclusion Criteria:

* CF as diagnosed by:

  1. Documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test; or
  2. Two well-characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
  3. Abnormal nasal potential difference with accompanying symptoms characteristic of CF.
* PA present in expectorated sputum or throat swab culture at Screening.
* Participants must have received three or more courses of TIS within the previous 12 months.
* Participants on chronic azithromycin must have had no change in regimen in the previous 3 months and must have had a need for TIS and/or additional antipseudomonal therapy since initiation of azithromycin.
* Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75% predicted at Screening.
* Ability to perform reproducible pulmonary function tests.
* Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.

Exclusion Criteria:

* Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day.
* History of sputum or throat culture swab yielding Burkholderia cepacia in the past 2 years.
* History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
* Administration of any investigational drug or device within 28 days of Screening (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).
* Known local or systemic hypersensitivity to monobactam antibiotics.
* Inability to tolerate inhalation of a short acting Beta-2 agonist.
* Changes in antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days before Screening or between Screening and the next visit.
* Changes in physiotherapy technique or schedule within 7 days before Screening or between Screening and the next visit.
* History of lung transplantation.
* A chest X-ray indicating abnormal findings at Screening or within the previous 90 days.
* Abnormal renal or hepatic function or serum chemistry at Screening (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] greater than 5 times the upper limit of normal range; Creatinine greater than 2 times the upper limit of normal range).
* Positive pregnancy test at Screening.
* Female of childbearing potential who was lactating or in the opinion of the investigator was not practicing acceptable birth control.
* Any serious or active medical or psychiatric illness, which in the opinion of the investigator would have interfered with participant treatment, assessment, or compliance with the protocol.
D: Inclusion Criteria:

* Acute or chronic disease requiring secretion mobilization as per hospital protocol

Exclusion Criteria:

* Absolute contraindications for positional changes
* Absolute contraindications for chest percussion
* Women visibly pregnant
* Previous enrollment in study
* Previous CPT or Vest treatment

Answer: A