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:

* Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride concentration \> 60 mEq/L and/or two well characterized disease causing CFTR gene mutations
* 14 years of age and older at enrollment
* Clinically stable at enrollment
* Ability to comply with medication use, study visits and study procedures
* FEV1 % predicted \> 40% \< 80 % as calculated by reference equations

Exclusion Criteria:

* Respiratory culture positive for: B. cepacia complex within past year or at screening
* Use of systemic corticosteroids within 30 days of screening
* Use of intravenous antibiotics or oral quinolones within 14 days of screening
* History of biliary cirrhosis, portal hypertension, or splenomegaly
* Other major organ dysfunction
* History of lung transplantation or currently on lung transplant list
* Supplemental oxygen therapy
* Oxygen saturation \< 95 % on room air
* Positive pregnancy test at screening
* Investigational drug use within 30 days of screening
* History of alcohol, illicit drug or medication abuse within 1 year of screening
* Acute respiratory symptoms
* Inability to take any form of bronchodilator
* Wheezing at the time of study
C: Inclusion Criteria:

* Males and females
* Age 7-12 years old
* Diagnosis of cystic fibrosis by sweat chloride \> 60 meq/L, or presence of two CFTR mutations known to cause CF
* Routinely treated with the short-acting bronchodilator albuterol
* FEV1 \> 90% of predicted values

Exclusion Criteria:

* FEV1 \< 90% of predicted values
* Routine use of hypertonic saline, mannitol, or amiloride
* Allergic bronchopulmonary aspergillosis (ABPA)
* Sputum colonization with Burkholderia cepacia or multiple antibiotic resistant organisms
* Evidence of a pulmonary exacerbation within past two weeks
* Treated with intravenous or oral antibiotics in the past two weeks for a pulmonary exacerbation
* Presence of an acute respiratory illness characterized by:

  * Coughing above baseline values
  * Wheezing
  * Respiratory distress
  * Hemoptysis
* Cannot perform the inhalation maneuvers that are required for drug inhalation or radioaerosol administration
D: Inclusion Criteria:

* Pass the inhalation test
* Chronic sputum production, at least ≥ 10 ml /24h
* Cystic Fibrosis (CF) diagnosed ( established by genotype or sweat sodium\>70 mmol/l or sweat chloride of\>60 mmol/l)
* Clinically stable at the time of recruitment (defined as no requirement for antibiotics or change in respiratory medication in the preceding 4 weeks)
* Trained in the use of autogenic drainage technique (at least 6 months)
* Inhaling hypertonic saline since at least 6 months
* To be able to provide written, informed consent and perform the protocol and the evaluations

Exclusion Criteria:

* Active massive hemoptysis during the previous 2 months
* Patient in transplantation or retransplantation list
* Patient already participating in another study at the same time

Answer: A