No clinical characteristics, particularly not sputum characteristics, can guide antibiotic prescription in patients with mild to severe COPD exacerbations
Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia. Mechanically ventilated patients are at risk of contracting pneumonia. Therefore, these patients often receive prophylactic systemic antimicrobial therapy. Intriguingly however, a previous study showed that antimicrobial activity in bronchoalveolar aspirates (here referred to as “sputa”) from ventilated patients was only partially explained by antibiotic therapy. Here we report that sputa from these patients presented distinct proteome signatures depending on the presence or absence of antimicrobial activity. Moreover, we show that the same distinction applied to antibodies against Streptococcus pneumoniae , which is a major causative agent of pneumonia. Specifically, the investigated sputa that inhibited growth of S. pneumoniae , while containing subinhibitory levels of the antibiotic cefotaxime, presented elevated levels of proteins implicated in innate immune defenses, including complement and apolipoprotein-associated proteins. In contrast, S. pneumoniae -inhibiting sputa with relatively high cefotaxime concentrations or noninhibiting sputa contained higher levels of proteins involved in inflammatory responses, such as neutrophil elastase-associated proteins. In an immunoproteomics analysis, 18 out of 55 S. pneumoniae antigens tested showed significantly increased levels of IgGs in inhibiting sputa. Hence, proteomics and immunoproteomics revealed elevated levels of antimicrobial host proteins or S. pneumoniae antigen-specific IgGs in pneumococcal growth-inhibiting sputa, thus explaining their anti-pneumococcal activity. IMPORTANCE Respiratory pathogens like Streptococcus pneumoniae can cause severe pneumonia. Nonetheless, mechanically ventilated intensive care patients, who have a high risk of contracting pneumonia, rarely develop pneumococcal pneumonia. This suggests the presence of potentially protective antimicrobial agents in their lung environment. Our present study shows for the first time that bronchoalveolar aspirates, “sputa,” of ventilated patients in a Dutch intensive care unit were characterized by three distinct groups of proteome abundance signatures that can explain their anti-pneumococcal activity. Importantly, this anti-pneumococcal sputum activity was related either to elevated levels of antimicrobial host proteins or to antibiotics and S. pneumoniae -specific antibodies. Further, the sputum composition of some patients changed over time. Therefore, we conclude that our study may provide a novel tool to measure changes that are indicative of infection-related conditions in the lungs of mechanically ventilated patients.
Chest physical therapy (CPT) is a widely used intervention for patients with airway diseases. The main goal is to facilitate secretion transport and thereby decrease secretion retention in the airways. Historically, conventional CPT has consisted of a combination of forced expirations (directed cough or huff), postural drainage, percussion, and/or shaking. CPT improves mucus transport, but it is not entirely clear which groups of patients benefit from which CPT modalities. In general, the patients who benefit most from CPT are those with airways disease and objective signs of secretion retention (eg, persistent rhonchi or decreased breath sounds) or subjective signs of difficulty expectorating sputum, and with progression of disease that might be due to secretion retention (eg, recurrent exacerbations, infections, or a fast decline in pulmonary function). The most effective and important part of conventional CPT is directed cough. The other components of conventional CPT add little if any benefit and should not be used routinely. Alternative airway clearance modalities (eg, high-frequency chest wall compression, vibratory positive expiratory pressure, and exercise) are not proven to be more effective than conventional CPT and usually add little benefit to conventional CPT. Only if cough and huff are insufficiently effective should other CPT modalities be considered. The choice between the CPT alternatives mainly depends on patient preference and the individual patient's response to treatment.
MULTIFILE
De chronische longziekte COPD (Chronic Obstructive Pulmonary Disease) kenmerkt zich door een toename van kortademigheid, hoesten en slijmvorming en is een veelvoorkomende ziekte in Nederland. Momenteel zijn er therapieën beschikbaar, waaronder het voorschrijven van een lage onderhoudsdosis Azitromycine, die ervoor zorgt dat het aantal longaanvallen drastisch daalt. De samenstelling van de microbiële populatie (het microbioom) in deze patiëntenpopulatie speelt een belangrijke rol in het ziekteverloop. Microvida analyseert COPD-patiëntmonsters voor het Amphia met behulp van klassieke kweektechnieken en wil nu haar dienstverlening graag uitbreiden. Nieuwe innovatieve ‘next-generation sequencing’ (NGS) maakt het mogelijk om het volledige microbioom van deze patiëntenpopulatie snel en gedetailleerd in kaart te brengen zonder kweek vooraf. Binnen dit project gaan we met een driehoek van MKB-, kennis- en praktijkpartners een high-throughput methode opzetten die het mogelijk maakt het microbioom in sputum snel en gebruiksvriendelijk te analyseren binnen deze patiëntenpopulatie. In het Amphia ziekenhuis loopt momenteel een klinische trial die het veilig afbouwen van het antibioticum Azitromycine onderzoekt en waarbij sputum samples verzameld worden. Met deze samples wordt in dit project een methode opgezet voor het isoleren van zuiver genetisch materiaal alvorens deze samples met behulp van NGS-technieken geanalyseerd worden. Als laatste stap zal een gebruikersinterface ontwikkeld worden die het mogelijk maakt om de verkregen data gebruiksvriendelijk te interpreteren en de resultaten te beoordelen. Alles met uiteindelijke doel meer kennis te vergaren over de samenstelling van het microbioom in relatie tot ziekte en gezondheid van de COPD-patiënt.
