Objective: To characterize FeNO levels that may be indicative of eosinophilic airway inflammation in patients with chronic obstructive airways disease

Number of participants: Approximately 200 subjects will be enrolled

Reference product: NIOX MINO® Instrument (09-1100)

Performance assessments: Fractional Exhaled Nitric Oxide (FeNO) Measurements will be performed according to the "Perform FeNO Measurement" guidelines on page 7 of the NIOX MINO® User Manual

Safety assessments: The Investigator is responsible for the detection, reporting, and documentation of events meeting the definition of an Adverse Event (AE) and/or Serious Injuries as provided in this clinical investigation plan from the time that informed consent has been provided and during the study period

Criteria for evaluations: This is an observational, pilot study and there are currently no plans for a formal statistical analysis. Information gained from this study may used to design subsequent studies in patients with chronic obstructive airways disease. Information collected will be summarized in a clinical study report but will not be subject to formal hypothesis testing

INTRODUCTION

Overview:

The measurement of exhaled nitric oxide (FeNO) is the only clinical test for measuring airway inflammation that can be performed consistently and accurately in clinical practice at the point-of-care. Airway inflammation is now recognized as the central mechanism in the pathogenesis of asthma and its symptoms. The measurement of FeNO with the NIOX MINO® device provides a rapid, noninvasive, and inexpensive tool to assess airway inflammation in inflammatory airway diseases such as asthma. The test is easy to perform and requires minimal training for the operator to conduct the test.

Burden of Disease:

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of diseases characterized by chronic airflow obstruction that interferes with normal breathing . The Centers for Disease Control and Prevention (CDC) reported that in the year 2005, approximately one in 20 deaths in the United States had COPD as the underlying cause.

Role of Exhaled Nitric Oxide (FeNO):

FeNO has evolved as a predictive and prognostic biomarker for airway inflammation. Nitric oxide (NO) gas is produced in the epithelial cells of the bronchial wall as an intrinsic part of the inflammatory process.

COPD can coexist with asthma. However, the exact role of FeNO in patients with established COPD remains to be the defined. While COPD airway inflammation is usually associated with increased neutrophils, some patients with COPD may have features of asthma such as a mixed inflammatory pattern with increased eosinophils. However, many patients have difficulty expectorating sputum and/or can only produce poor quality sputum samples which are not adequate to accurately quantify eosinophilic cells. Since FeNO can be measured easily and reliably, it may be useful in evaluating airway inflammation in COPD and thus predicting steroid responsiveness in COPD.

Intended Use:

NIOX MINO® measures Nitric Oxide (NO) in human breath. Nitric Oxide is frequently increased in inflammatory processes such as asthma. The fractional NO concentration in expired breath (FeNO) can be measured by NIOX MINO® with assurance that such measurements are repeatable and according to guidelines for NO measurement established by the American Thoracic Society.

Rationale for Study:

While there have been a number of preliminary studies on FeNO in COPD, literature defining the role of FeNO in patients with established COPD is minimal. The purpose of the current study, therefore is to characterize FeNO levels that may be indicative of eosinophilic airway inflammation in patients with chronic obstructive airways disease. This data may be useful in determining whether or not FeNO can predict improvement in FEV1 following ICS treatment

CLINICAL INVESTIGATION OBJECTIVES To characterize FeNO levels that may be indicative of eosinophilic airway inflammation in patients with chronic obstructive airways disease.

CLINICAL INVESTIGATION PLAN

This is a pilot, observational, multi-center, single-visit, outpatient study. Subjects meeting all of the Inclusion Criteria and none of the Exclusion Criteria, and who express interest in study participation, will be asked to provide the following documentation and information:

• Informed Consent

• Demographics

• Baseline Characteristics

• FeNO:

  - Subjects will receive training by the study staff on use of the NIOX MINO® device to perform FeNO Measurements

• Spirometry

• Severity of COPD

Subject discharge from the study:

Once all information has been collected and all procedures have been performed, the subject will be discharged from the clinic and their study participation will be complete

Selection of investigation population:

Male and female subjects, age 40 years and above, inclusive, with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and emphysema and/or a mixed diagnosis of asthma/COPD will be recruited. A subject should be withdrawn from the clinical investigation if, in the opinion of the Investigator, it is medically necessary, or if it is the expressed wish of the subject.

Medical device:

The NIOX MINO® was initially cleared by the FDA on March 4, 2008 as a new hand-held device for the measurement of exhaled Nitric Oxide, a marker of eosinophilic airway inflammation. The most recent clearance by the FDA was on September 2, 2010 for Instrument (09-1100), which will be used in this study. NIOX MINO® can be used in children 7-17 years of age and in adults 18 years of age or older in the initial assessment and management of asthma.

The NIOX MINO® is a 10 second test based on exhaled breath measured at a 50 ml/second flow rate. Results are provided at the point of care within 2 minutes after the successful completion of the breath test. The test cannot be influenced by patient effort or variations in the clinician's test technique.

Definitions:

Adverse event: Any incident where the use of a medical device (including in vitro diagnostics) is suspected to have resulted in an adverse outcome in a patient.

Serious Injury means injury or illness that:

• Is life-threatening
• Results in permanent impairment of a body function or permanent damage to a body structure, or
• Necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.

Malfunction: the failure of a device to meet its performance specifications or otherwise perform as intended.

Caused or contributed: the death or serous injury was or may have been attributed to a medical device, or that the medical device was or may have been a factor in a death or serious injury, including events occurring as a result of:

• Failure
• Malfunction
• Improper or inadequate design
• Manufacture
• Labeling
• User error

Inclusion Criteria:

• Diagnosis: Chronic obstructive pulmonary disease (COPD) including chronic bronchitis and emphysema, and/or a mixed diagnosis of asthma/COPD.

Exclusion Criteria:

• Concurrent Conditions or Disease: Subjects with other chronic obstructive lung diseases including but not limited to cystic fibrosis (CF), bronchiectasis, obliterative bronchiolitis, ciliary dyskinesia, post-viral bronchial hyperresponsive syndrome, vocal cord dysfunction, rhinosinusitis, non-eosinophilic asthma, and reactive airways dysfunction syndrome are excluded. In addition, subjects with pneumothorax, fractured rib(s), or signs of cardiac instability including but not limited to a recent myocardial infarction, unstable angina, unstable vital signs, or acute shortness of breath, chest tightness or chest pain are excluded.
• Study Participation Outside of This Protocol: Subjects currently enrolled in studies of Investigational or non-Investigational Drugs or Medical Devices and/or who participated in these studies within 30 days prior to this study are excluded.

Patients from the UNC Hospital Outpatient Pulmonary Function Laboratory in Chapel Hill, NC and approximately 3 to 6 outpatient clinics associated with UNC who meet the inclusion/exclusion criteria