Screening for Chronic Obstructive Pulmonary Disease in Patients With Acute Coronary Syndromes
Condition: Chronic Obstructive Pulmonary Disease; Acute Coronary Syndromes
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Acute Coronary Syndrome; Syndrome
Study type: Interventional

Summary: 
      Several studies and registries suggested that the concomitant presence of acute coronary
      syndromes (ACS) and chronic obstructive pulmonary disease (COPD) is significantly associated
      with poor prognosis. It has been suggested that diagnosis of COPD is frequently missing.
      Thus, it is plausible that a significant percentage of patients with ACS may have
      unrecognized COPD. This missing diagnosis may contribute significantly to poor prognosis. The
      investigators suppose that the concomitant use of peak expiratory flow (PEF) measurement and
      of Respiratory Health Screening Questionnaire (RHSQ, adapted version) could be useful as
      screening test for COPD in patient smokers or former smokers admitted to hospital with a
      diagnosis of ACS. In all screened patients COPD diagnosis will be confirmed (or not) two
      months after hospital discharge with spirometry. In the same setting of patients, the
      investigators will characterize the underlying pathological mechanisms, evaluating several
      inflammation, platelet and endothelial markers.
    

Detailed description: 
      BACKGROUND:

      Acute coronary syndromes (ACS) and chronic obstructive pulmonary disease (COPD) are
      respectively the first and the fourth leading cause of death in Western countries. ACS and
      COPD shared several risk factor, in particular smoking habitus. Available data may be
      summarized as follows: i) ACS, and generally ischemic heart disease (IHD), are the most
      frequent comorbidity in COPD patients; ii) cardiac adverse events are the most frequent cause
      of hospitalization and/or death in COPD patients; iii) patients with ACS and concomitant COPD
      are at higher risk of mortality, re-infarction and heart failure (HF); iv) COPD is frequently
      undiagnosed in patients with IHD. At the best of our knowledge, no studies investigated the
      effectiveness and feasibility of screening procedures to early detect COPD in ACS patients.
      The identification of unrecognized COPD in ACS patients may permit an optimization of the
      treatment with an significant improvement in the outcome. Finally, it is well known that
      several biological processes are involved in the development and worsening of IHD-COPD
      comorbidity (e.g. inflammation, hypoxia, heightened platelet reactivity, endothelial
      dysfunction). Nevertheless, a complete evaluation of these processes is currently missing. A
      better characterization of these biological processes underlying the ACS-COPD comorbidity may
      significantly improve its management.

      HYPOTHESIS and SIGNIFICANCE:

      Based on previous studies in patients with stable IHD, we suppose that at least 30% of
      patients admitted to hospital for ACS have undiagnosed COPD. They represent a subgroup of
      patients at very high risk of death, reinfarction and heart failure. We hypothesize that the
      combined use of PEF and RHSQ (adapted version) in ACS patients (smokers or former smokers)
      before hospital discharge may discriminate those with undiagnosed COPD. The early diagnosis
      of COPD comorbidity may have important clinical implications. We speculate that early
      identification of undiagnosed COPD in ACS patients may permit a promptly treatment and
      improve outcomes. Finally, we suppose that the worst outcome observed in ACS patients with
      undiagnosed COPD as well as in patients with prior ACS and acute exacerbation of COPD is due
      to a specific pattern of alterations in platelet reactivity (PR), endothelial function (EF)
      and inflammation. Therefore, their characterization may lead to an improvement in the
      clinical management of these patients.

      METHODS:

      Blood samples: At the time of enrollment an aliquot (7-10 ml) of whole blood will be
      collected and stored for DNA and RNA extraction. Blood samples to obtain plasma (7-10 ml) and
      serum (7-10 ml) will be collected both at the timing of enrolment and at the time of
      spirometry.

      Screening procedure: PEF and RHSQ (adapted version) will be administered by an independent
      combined team of cardiologist and pulmonologist before the hospital discharge. According to
      international guidelines, patients will be asked to perform 3 consecutive PEF measurements
      and the highest values will be recorded. A PEF value below 80% predicted will be considered
      predictive of impaired lung function. The RHSQ questionnaire will be performed as previously
      reported with a value >19 suggesting high probability of COPD.

      Spirometry: spirometry test will be performed 50-70 days after hospital discharge (enrollment
      time).

      Primary outcome of the study: the endpoint of the study is the diagnosis of COPD at
      spirometry. The aim of the study is to establish if the combined use of PEF and RHSQ
      questionnaire is able to early predict COPD diagnosis.

      Clinical follow-up: a complete 1-year follow-up will be collected in each patient recording
      the occurrence of all adverse events and hospital admissions. All adverse events will be
      adjudicated by two independent reviewers blinded to screening and spirometry outcomes.

      Biological parameters: several evaluations of inflammation, endothelial and platelet function
      markers will be performed in blood samples from patients. The principals are reported below:
      high sensitivity C-reactive protein, fibrinogen, interleukin (IL)-6, IL-1Ra, tumor necrosis
      factor (TNF)-alpha, platelet reactivity as assessed by light transmission aggregometry and
      VerifyNow system, ICAM and Bcl-2 and e-NOS (extracellular nitric oxide synthase) (in human
      umbilical vein endothelial cells that will be incubate with serum of patients), intracellular
      levels of reactive oxygen species.

      Secondary outcomes: PEF, RHSQ, biological parameters and spirometry results will be related
      to clinical outcome.
    

Intervention name(s): screening test
Intervention type(s): Other
Intervention description(s): screening test with peak expiratory flow and respiratory health screening questionnaire to discriminate patients at risk for COPD
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: screening procedure; peak expiratory flow; respiratory health screening questionnaire