Pulmonary CT in Pneumonia Complicating Stroke

Feasibility and Reliability of Pulmonary Computed Tomography as a Radiological Reference Standard for Evaluating Chest X-ray and Candidate Biomarkers in Suspected Pneumonia Complicating Stroke

Pneumonia commonly complicates stroke and has a profound impact on clinical outcomes. Accurate and timely diagnosis of pneumonia complicating stroke remains a major challenge as several issues potentially confound diagnosis. Chest X-ray (CXR), a central component in the diagnostic work-up, may have limited utility in the early stages as they are often of suboptimal quality, and infrequently confirm typical diagnostic infiltrates. Blood biomarkers of the stress-immune response have received considerable attention, but interpretation has been limited by differing methodologies, including definition of pneumonia. Bacterial organisms in the oral cavity may also be of relevance as biomarkers of post-stroke pneumonia. Major challenges facing frontline clinicians are therefore whether to initiate antibiotics; if so, when and for how long. These issues have antibiotic stewardship implications for clinicians in terms of potential for under-treatment or over-treatment with antibiotics based on CXR appearances.

Pulmonary Computed Tomography (CT) could be of value as a radiological reference standard when pneumonia is suspected after stroke, and enable more rigorous evaluation of the diagnostic performance of CXR (and other candidate biomarkers) to inform decision-making when pneumonia is suspected.

The overall primary aim is therefore to investigate the feasibility and reliability of using pulmonary CT as a radiological reference standard for evaluating suspected pneumonia complicating stroke. The secondary aims are to explore the diagnostic accuracy of CXR and blood biomarkers (index tests) when pneumonia is suspected during hospital admission after stroke using pulmonary CT as a reference standard.

Study Overview

• Status: Completed
• Conditions: Stroke; Pneumonia
• Intervention / Treatment: Radiation: pulmonary computed tomography (CT)

Detailed Description

Pneumonia is a frequent complication of stroke, particularly within the first few days. The risk of pneumonia is increased in patients who are older, have a more severe stroke and in those who have swallowing problems as a result of their stroke. Patients who develop pneumonia have a higher risk of death and longer hospital stay. The diagnosis of pneumonia is not always easy, but it is important to identify pneumonia early in order to begin the most appropriate treatment in a timely fashion and avoid giving antibiotics unnecessarily. Chest x-ray, the standard test undertaken when pneumonia is suspected, infrequently shows changes and is of limited value.

Pulmonary Computed Tomography (CT) scans can be used to image the lungs in more detail than a standard chest xray. The Investigators plan to assess if it is feasible to perform pulmonary CT imaging in stroke patients within 48 hours of symptoms and who may be acutely unwell. The Investigators will also investigate how reliable CT is at diagnosing pneumonia by asking different x-ray doctors to review the scans. Comparing the result of the pulmonary CT imaging to the chest x-ray will allow assessment of their utility for the diagnosis of pneumonia. The Investigators will also record whether the CT informs clinical management e.g. stopping antibiotics if pneumonia is excluded.

Blood samples will be collected for measurement of inflammatory markers and mouth swabs will measure types of bacteria. The analysis will be conducted at Salford Royal NHS Foundation Trust (SRFT) and using new cutting-edge techniques performed by collaborators at ThermoFisher and Manchester Collaborative Centre for Inflammation Research. The Investigators will assess how useful these inflammatory proteins are in pneumonia diagnosis compared to the pulmonary CT scans. This research will help the Investigating team design larger studies to diagnose pneumonia earlier and more accurately, enabling more effective use of antibiotics.

• Study Type: Observational
• Enrollment (Actual): 41

Contacts and Locations

Study Locations

• United Kingdom
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Salford Royal NHS Foundation Trust
  • Staffordshire
    • Stoke on Trent, Staffordshire, United Kingdom, ST4 6QG
      • Royal Stoke University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Inpatient stroke service at Salford Royal Foundation Trust (SRFT) and Royal Stoke University Hospital (RSUH)

Description

Inclusion Criteria:

• Inpatient in SRFT or RSUH with diagnosis of stroke current admission
• Within 24h of clinically suspected pneumonia occurring after admission
• Aged ≥18y
• Provision of informed consent from participant or personal consultee
• Able to undergo pulmonary CT within next 48h

Exclusion Criteria:

• Treatment for lower respiratory tract infection (LRTI) completed within the preceding month
• Mechanical ventilation planned or anticipated imminently
• End-of-life care planned or anticipated imminently

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportions of eligible participants from screening; eligible participants declining participation (and reasons)		18 months
Proportion of participants undergoing pulmonary CT	Participants scanned and reasons for not scanning	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of consenting participants undergoing repeat CXR when indicated		18 months
Proportion with changes consistent with pneumonia on CXR; proportion with changes consistent with pneumonia on pulmonary CT		18 months
Proportion participants with changes consistent with pneumonia on pulmonary CT		18 months
Characteristics and distribution of radiological changes consistent with pneumonia on pulmonary CT	Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values	18 months
Spectrum of additional radiological findings on pulmonary CT		18 months
Inter-rater reliability of CXR; and pulmonary CT interpretation	Inter-rater reliability of the CXR reports will be evaluated using k statistics and the Bland and Altman method	3 months
Inter-rater reliability of pulmonary CT interpretation	Inter-rater reliability of the pulmonary CT reports will be evaluated using k statistics and the Bland and Altman method	3 months
Proportion of participants with confirmed pneumonia	Confirmed pneumonia is defined as meeting the PISCES clinical criteria AND with changes of pneumonia on pulmonary CT, agreed by an adjudication panel	18 months
Estimate and confidence intervals of sensitivity and specificity of CXR	Using diagnostic odds ratio for CXR singly and with repeat CXR where indicated clinically	3 months
Estimate and confidence intervals of sensitivity and specificity of C-reactive protein (CRP) markers	Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values	18 months
Estimate and confidence intervals of sensitivity and specificity of procalcitonin (PCT)	Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values	18 months
Estimate and confidence intervals of sensitivity and specificity of copeptin	Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values	18 months
Estimate and confidence intervals of sensitivity and specificity of pro-adrenomedullin (Pro-ADM)	Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values	18 months
Estimate and confidence intervals of sensitivity and specificity of monocyte/ B-cell markers	Using standard assessments of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values	18 months
Characteristics of oral bacterial species	Oral bacterial species will be compared in patients with and without confirmed pneumonia in univariate hypothesis generating analyses	18 months
Distribution of oral bacterial species	Oral bacterial species will be compared in patients with and without confirmed pneumonia in univariate hypothesis generating analyses	18 months
Number of days of antibiotic treatment		18 months

Collaborators and Investigators

• Sponsor: Natalie Garratt
• Investigators: Principal Investigator: CRAIG SMITH, Northern Care Alliance NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2017
• Primary Completion (Actual): July 31, 2018
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: April 4, 2017
• First Posted (Actual): April 11, 2017

Study Record Updates

• Last Update Posted (Actual): February 7, 2020
• Last Update Submitted That Met QC Criteria: February 6, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: stroke; biomarkers; pneumonia; pulmonary CT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Stroke; Pneumonia
• Other Study ID Numbers: 213436

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD will not be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No