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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.

Cough is a very common symptom in the community, and lower respiratory tract infections (LRTIs) occur very frequently in all seasons. The primary goal in the diagnostic work-up of LRTI is to differentiate serious conditions like community acquired pneumonia (CAP) from self-limiting conditions and to prevent unnecessary prescribing of antibiotics. To improve diagnostic accuracy additional diagnostic testing is potentially useful. A promising additional test is C-reactive protein (CRP). A point-of-care (POC) test in capillary blood yields CRP results within a few minutes, and can thus be applied in decision making (whether or not to prescribe antibiotics) during consultation. POC CRP testing was introduced in Dutch primary care after incorporation in the guideline LRTI of the Dutch College of General Practice in 2011. So far, little is known about the compliance of GPs with these guidelines and the impact of POC CRP introduction on prescription of antibiotics for LRTI. This thesis aimed to evaluate optimal use of the point-of-care (POC) C-reactive protein (CRP) in primary care and its impact in day-to-day practice. More specifically our aims were to determine: [1] the (added) diagnostic value of CRP in the diagnostic work-up of community acquired pneumonia (CAP) in primary care, [2] the suitability of POC CRP test devices for primary care and [3] the impact of the POC CRP test result on the general practitioner’s (GP) decision to prescribe antibiotics. The first part of this thesis showed that a prediction model including coryza, dyspnoea, crackles, diminished breath sounds, fever, and tachycardia, had the best diagnostic performance in diagnosing CAP. Moreover, adding CRP to signs and symptoms in the diagnostic workup of CAP improved both discrimination and risk classification. Nevertheless, in the majority of patients uncertainty about the diagnosis remained after adding CRP, because their predicted risk of CAP after application of the risk model remained in the ‘intermediate’ range. The second part of this thesis showed that five different POC CRP test devices show considerable variation in analytical performance and agreement with a laboratory reference test. These differences do not translate into differences in accuracy of predicting (radiographic) CAP, both as single test as well as in combination with available clinical findings. In the third part of this thesis we concluded that implementation of POC CRP testing did not reduce overall antibiotic prescribing for patients presenting with acute cough. Moreover, only a minority of patients who underwent POC CRP testing had an indication for testing according to guideline recommendations. The POC CRP test result did influence the GPs’ decision making to prescribe antibiotics in nearly one third of all cases. Finally, only a quarter of all eligible patients were recruited in our implementation study, which resulted in overestimation of POC CRP test use, antibiotic prescribing and in an overestimation of the effects of POC CRP test use on antibiotics prescribing.