Lower respiratory tract infection in the community: associations between viral aetiology and illness course

Objectives: This study determined associations between respiratory viruses and subsequent illness course in primary care adult patients presenting with acute cough and/or suspected lower respiratory tract infection.Methods: A prospective European primary care study recruited adults with symptoms of lower respiratory tract infection between November 2007 and April 2010. Real-time in-house polymerase chain reaction (PCR) was performed to test for six common respiratory viruses. In this secondary analysis, symptom severity (scored 1 = no problem, 2 = mild, 3 = moderate, 4 = severe) and symptom duration were compared between groups with different viral aetiologies using regression and Cox proportional hazard models, respectively. Additionally, associations between baseline viral load (cycle threshold (Ct) value) and illness course were assessed.Results: The PCR tested positive for a common respiratory virus in 1354 of the 2957 (45.8%) included patients. The overall mean symptom score at presentation was 2.09 (95% confidence interval (CI) 2.07-2.11) and the median duration until resolution of moderately bad or severe symptoms was 8.70 days (interquartile range 4.50-11.00). Patients with influenza virus, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), coronavirus (CoV) or rhinovirus had a significantly higher symptom score than patients with no virus isolated (0.07-0.25 points or 2.3-8.3% higher symptom score). Time to symptom resolution was longer in RSV infections (adjusted hazard ratio (AHR) 0.80, 95% CI 0.65-0.96) and hMPV infections (AHR 0.77, 95% CI 0.62-0.94) than in infections with no virus isolated. Overall, baseline viral load was associated with symptom severity (difference 0.11, 95% CI 0.06-0.16 per 10 cycles decrease in Ct value), but not with symptom duration.Conclusions: In healthy, working adults from the general community presenting at the general practitioner with acute cough and/or suspected lower respiratory tract infection other than influenza impose an illness burden comparable to influenza. Hence, the public health focus for viral respiratory tract infections should be broadened. (C) 2020 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Diagnostic strategies for chronic obstructive pulmonary disease

Adequate detection of chronic obstructive pulmonary disease (COPD) in patients who present with persistent cough in general practice is highly warranted, because targeted interventions for COPD (notably smoking cessation programmes) improve the quality of life. Nevertheless, much is unknown about the diagnostic value of tests that are usually included in the diagnostic workup in suspected COPD in primary care, including symptoms and signs. Whether and to what extent COPD can be excluded or diagnosed by history taking and physical examination is unknown, as is the added diagnostic value of spirometry by general practitioners (GPs). The independent value of other potentially useful diagnostic tests, such as level of C-reactive protein (CRP) and reversibility testing after an oral corticosteroid test, has also never been reported. Persistent cough is one of the most frequent complaints in general practice which underlines that diagnostic strategies for COPD in these patients should be efficient and evidence based. The study aims of this thesis were to quantify the diagnostic value of different (combinations of) diagnostic tests in middle aged and elderly patients suspected of COPD, i.e., those consulting their GP because of persistent cough. 400 patients were included in a diagnostic study in the Netherlands performed between 2006 and 2009. They underwent an extensive diagnostic work-up for COPD, including standardised history taking and physical examination, as well as secondary care lung function tests. An expert panel finally determined the presence or absence of COPD (reference test), and found that 118 patients (30 %) had COPD. History taking and physical examination items with independent diagnostic value were increasing age, male gender, current smoking, > 20 pack years of smoking, a history of cardiovascular disease, wheezing complaints, diminished breath sounds and wheezing on auscultation. A multivariable score combining these items was accurate for excluding COPD (the negative predictive value of a low score was 92 %). This score had additional diagnostic value beyond the physician’s own initial clinical estimation of the probability of COPD. Adding spirometry results obtained by the GP to the before mentioned history and physical examination substantially improved diagnostic risk classification for COPD. CRP levels on the other hand had no clinically relevant added value. The diagnostic value of a prednisolone test for excluding or diagnosing COPD was also studied in 233 study patients with persistent cough. All subjects used a 14 day prednisolone test of 30 milligram per day including before and after measurement of the post bronchodilator forced expiratory volume in one second (FEV1). The prednisolone test result was defined positive if the FEV1 exceeded 200 ml or 12 % of the baseline value. A positive test result was associated with COPD, but had no value in addition to more easily obtainable diagnostic information. In the general discussion, implications for clinical practice and future research, in the view of our main finding were debated

Diagnostic properties of C-reactive protein for detecting pneumonia in children

BACKGROUND: The diagnostic value of C-reactive protein (CRP) level for pneumonia in children is unknown. As a first step in the assessment of the value of CRP, a diagnostic study was performed in children at an emergency department (ED). METHODS: In this cross-sectional study, data were retrospectively collected from children presenting with suspected pneumonia at the ED of Antonius Hospital Nieuwegein in The Netherlands between January 2007 and January 2012. Diagnostic outcome was pneumonia yes/no according to independent radiologist. (Un)adjusted association between CRP level and pneumonia and diagnostic value of CRP were calculated. RESULTS: Of 687 presenting children, 286 underwent both CRP measurement and chest radiography. 148 had pneumonia (52%). The proportion of pneumonia increased with CRP level. Negative predictive values declined, but positive predictive values increased with higher CRP thresholds. Univariable odds ratio for the association between CRP level and pneumonia was 1.2 (95% CI 1.11-1.21) per 10 mg/L increase. After adjustment for baseline characteristics CRP level remained associated with pneumonia. CONCLUSIONS: CRP level has independent diagnostic value for pneumonia in children presenting at the ED with suspected pneumonia, but low levels do not exclude pneumonia in this setting. These results prompt evaluation of CRP in primary care children with LRTI

Use of expert panels to define the reference standard in diagnostic research : a systematic review of published methods and reporting

BACKGROUND: In diagnostic studies, a single and error-free test that can be used as the reference (gold) standard often does not exist. One solution is the use of panel diagnosis, i.e., a group of experts who assess the results from multiple tests to reach a final diagnosis in each patient. Although panel diagnosis, also known as consensus or expert diagnosis, is frequently used as the reference standard, guidance on preferred methodology is lacking. The aim of this study is to provide an overview of methods used in panel diagnoses and to provide initial guidance on the use and reporting of panel diagnosis as reference standard. METHODS AND FINDINGS: PubMed was systematically searched for diagnostic studies applying a panel diagnosis as reference standard published up to May 31, 2012. We included diagnostic studies in which the final diagnosis was made by two or more persons based on results from multiple tests. General study characteristics and details of panel methodology were extracted. Eighty-one studies were included, of which most reported on psychiatry (37%) and cardiovascular (21%) diseases. Data extraction was hampered by incomplete reporting; one or more pieces of critical information about panel reference standard methodology was missing in 83% of studies. In most studies (75%), the panel consisted of three or fewer members. Panel members were blinded to the results of the index test results in 31% of studies. Reproducibility of the decision process was assessed in 17 (21%) studies. Reported details on panel constitution, information for diagnosis and methods of decision making varied considerably between studies. CONCLUSIONS: Methods of panel diagnosis varied substantially across studies and many aspects of the procedure were either unclear or not reported. On the basis of our review, we identified areas for improvement and developed a checklist and flow chart for initial guidance for researchers conducting and reporting of studies involving panel diagnosis. Please see later in the article for the Editors' Summary