Year in review 2016: Respiratory infections, acute respiratory distress syndrome, pleural diseases, lung cancer and interventional pulmonology (2017)

Marcos I. Restrepo and James D. Chalmers Respirology has made important contributions related to respiratory infections over the past year. In this review, we focus on bronchiectasis, pneumonia, tuberculosis and non-tuberculous mycobacteria (NTM) infections as the most relevant topics in the area of respiratory diseases. Park et al. reported a study of 155 patients with bronchiectasis to identify the predictors of radiological progression of the disease.1 Treatment in bronchiectasis aims to reduce inflammation and airway infection to prevent further lung damage.2 Therefore, identifying the drivers of poor outcome is important. In this analysis, older patients, those with lower BMI and patients infected with Pseudomonas aeruginosa or NTM were more likely to show radiological progression, measured using the Bhalla score.1 In multivariable analysis, only P. aeruginosa and BMI were statistically significant. The results are supported by existing literature. P. aeruginosa colonization and BMI are both incorporated into the bronchiectasis severity index, a validated prediction tool, and P. aeruginosa in particular is strongly associated with other indicators of progression such as quality of life (QOL), forced expiratory volume in 1 s (FEV1), exacerbation frequency and mortality.3, 4 However, the most important step in the treatment of bronchiectasis is identifying the underlying cause, as many causes such as NTM infection, rheumatoid arthritis, primary ciliary dyskinesia, immunodeficiency or allergic bronchopulmonary aspergillosis require specific treatments.5, 6 Gao et al.7 conducted a systematic review into the underlying causes of bronchiectasis identified in 56 studies (n = 8608).7 The study was limited by the high variability in testing across different studies, and the variable definitions used, but was able to suggest that 18.3% of bronchiectasis patients have an aetiology with a specific treatment.7 Among the different respiratory infection papers published in Respirology, the vast majority were in the area of pneumonia as evidence of this important healthcare priority. We now summarize the most relevant contributions to the journal, focusing on the mechanism of disease secondary to infection, the controversial issue of microbiological diagnosis, biomarkers, treatment, health-related outcomes and complications of patients with pneumonia. Tang et al.8 showed that neutrophils from patients with asthma release C-X-C ligand 8 (CXCL8), neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in response to viral surrogates. In addition, Toll-like receptor (TLR7/8) dysregulation may play a role in neutrophilic inflammation in viral-induced exacerbations. This evidence suggest that neutrophils carry important immunological properties to directly detect and respond to both viral and bacterial pathogens.8 In addition, out of the three respiratory viruses including rhinovirus, influenza and respiratory syncytial virus (RSV), only RSV was able to activate neutrophils.8 The neutrophil activation and inflammation observed in asthma may be the result of the complex interactions between infectious pathogens and airway epithelium and smooth muscle.8 The authors also suggest that it may not be only the neutrophil activation that plays the leading role during exacerbations, but also the resolution or regulation of neutrophilic inflammation following infection.8 In an Editorial, Vlahos and Bozinovski9 suggest that neutrophils do indeed play an important role in the immune response of patients with asthma. The presence of overactivation of neutrophils during exacerbations increases asthma disease severity and emphasizes the different mechanisms by which neutrophils may contribute to the exacerbation period or the resolution period.9 Appropriate antimicrobial therapy and antimicrobial stewardship require knowledge of the underlying causative pathogen of community-acquired pneumonia (CAP). Several studies published in Respirology attempted to address the issue about the aetiology in patients with CAP. Sahuquillo-Arce et al. used a large Spanish data set to examine the impact of age on the aetiology of CAP.10 The study found that older patients were more likely to have Gram-negative infection, particularly with Haemophilus influenzae and enteric Gram-negative organisms. Co-morbidities were as, or more important than age, with diabetes being associated with pneumococcal and Staphylococcus aureus pneumonia and COPD associated with H. influenzae.10 The study confirms previous reports and points to the increasing problem of the ageing population changing the microbiology of CAP towards an increase in Gram-negative organisms.10 Along with an ageing population, there is also an expansion of patients receiving immunosuppressive drugs, such as patients receiving chemotherapy for malignancy.11 Guidol et al.12 studied 1723 patients with bacteraemia which included 795 patients with neutropenia and underlying malignancy. The most frequent cause was P. aeruginosa and the mortality rate was 46.2%. 12.8% of Gram-negative organisms identified were multidrug resistant.12 This study again emphasizes the need to consider unusual or resistant organisms in patients with immunosuppression.12 Metersky et al.13 presented data from the large USA Veterans Hospital database from 2002 to 2012, and found that a small proportion of patients with risk factors for healthcare-associated pneumonia (HCAP) had Pseudomonas pneumonia (1.9%) and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia (1.0%). In order to stratify who had one pathogen or the other, the authors suggest that MRSA pneumonia patients were more likely to be males, elderly (age >74 years), diabetics, have COPD, recent nursing home or hospital stay, recent exposure to fluoroquinolone or antibiotics treating Gram-positive organisms and severe pneumonia. In addition, patients with Pseudomonas pneumonia were more likely to have a prior hospitalization, immunosuppression, COPD, hemiplegia, recent exposure to inhaled corticosteroids, beta-lactam/cephalosporin/carbapenem antibiotics, antibiotics against Gram-positive organisms, ‘other antibiotics’ and severe pneumonia requiring intensive care unit (ICU) admission, vasopressors or use of invasive ventilation within 48 h of hospital admission.13 These results suggest that the appropriate selection of antibiotics may be driven by identifying the characteristics of patients with HCAP due to Pseudomonas or MRSA. In an elegant Editorial, Waterer14 suggest that the key aspect of antibiotic utilization is to know whether the pathogen causing pneumonia is present at the time of evaluation, rather than identifying whether the patients have HCAP or not. In addition, Dr Waterer14 stresses the point that these pathogen-specific risk factors had a positive or negative predictive value sufficient to reliably determine empiric antibiotic therapy as also recently pointed out in the literature.15 Cillóniz et al.16 presented an elegant review manuscript emphasizing the importance and clinical relevance of polymicrobial infections as the cause of CAP. The authors suggest that polymicrobial infection is an understudied and growing entity with distinct inflammatory, host response and disease-related characteristics that differ from other patients with CAP.16 Rapid identification of pathogens is the best solution to this problem. Diagnosis within hours using PCR or similar methods is not yet fully established, but matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALTI-TOF MS) is now in use in many centres to give a more rapid identification of pathogens. Mok et al.17 examined the impact of MALTI-TOF on their practice in severe pneumonia, showing that identification of pathogens from bronchoalveolar lavage in severe CAP, hospital-acquired pneumonia and ventilator-associated pneumonia was more rapid with MALTI-TOF resulting in earlier de-escalation of antibiotics.17 Specific pathogens can usually not be identified from their presenting features alone. Two papers reported on the characteristics of less frequently identified pathogens in CAP. An organism increasingly identified in hospital-acquired pneumonia is Acinetobacter baumannii and its related pathogens. It is frequently multidrug resistant and is a challenge globally. Özvatan et al.18 reported on 356 adult patients from Turkey of whom the large majority had ventilator-associated pneumonia. Mortality was high (53.1% at 30 days) and reduced by combination antibiotic therapy. Adenovirus is an unusual pathogen in immunocompetent CAP patients, but Yoon et al.19 reported a large case series of 91 patients with adenovirus pneumonia compared with 55 patients without adenovirus detected. Not surprisingly, there were no clinical features that could accurately identify an adenoviral pneumonia. The authors showed that adenovirus can be associated with the broad spectrum of disease, from mild CAP to CAP in the ICU.19 Monocytopenia was the only factor found to be clearly different between adenoviral and non-adenoviral CAP.19 Legionnaires disease is a relatively common cause of CAP, accounting for 1–10% of patients outside of epidemics.20, 21 While Legionella pneumophila is most frequently encountered worldwide, Isenman et al.22 provided a timely reminder that Legionella longbeachae is the predominant cause in some regions including parts of Australasia.22 The disease presents similarly to pneumophila, with a middle age to elderly male predominance, diarrhoea, myalgia, hyponatraemia and abnormal liver function tests—the classical features of Legionnaires disease, all common. Admission to the ICU was common at 25% but outcomes were relatively good if appropriate antibiotics were used.22 Procalcitonin (PCT) is thought to be a useful marker when trying to decide whether to withhold antibiotics from low-risk patients with respiratory infections. Ito et al. tested whether PCT could be used to predict mortality. Ito et al. 23 found that C-reactive protein, PCT and confusion, urea > 7 mmol/L, respiratory rate ≥ 30 breaths/min, low blood pressure (systolic < 90 mm Hg or diastolic ≤ 60 mm Hg) and age ≥ 65 years (CURB-65) were predictive of 30-day mortality, and PCT was additive to CURB-65. In addition to markers of systemic inflammation, the journal presented data on markers of coagulation in pneumonia with the latest in series from Cangemi et al.24 They showed in 104 patients that multiple markers of thrombosis were altered in acute pneumonia with evidence of prothrombotic state. This may contribute to the excess risk of cardiovascular disease that is consistently reported in patients with CAP.25 Another study published by Liu et al.26 presented a systematic review and meta-analysis that evaluated the prognostic value of PCT in patients with pneumonia. The authors identified 21 studies with 6007 patients in which high PCT levels were associated with an increased risk of death among patients with low severity of illness score according to a low CURB-65 score and critically ill patients.26 In addition, this study questions the use of the PCT cut-off value of 0.5 ng/mL due to the low sensitivity and the inability to recognize patients at risk of death.26 Finally, the study suggested that there are no differences in the PCT performance characteristics between patients with CAP and ventilator-associated pneumonia.26 Beta-lactam plus macrolides have become the standard of care for the management of patients with CAP. Horita et al.27 performed a systematic review and meta-analysis evaluating whether beta-lactam plus macrolide antibiotics lead to better survival than beta-lactam alone in patients with CAP. The authors included 14 studies, two open-label randomized controlled trials (RCTs) comprising 1975 patients, one non-RCT interventional study comprising 1011 patients and 11 observational studies comprising 33 332 Horita et al.27 found that CAP patients with beta-lactam plus macrolide compared with beta-lactam alone had a lower death with However, in the of patients with severe CAP, the use of combination therapy had a for mortality compared with beta-lactam antibiotic therapy Therefore, the suggested of combination therapy with macrolides observed in the severe CAP data are limited by the of observational studies identified in this systematic et performed a to the clinical of as treatment for adult patients with influenza The was from that suggested a mortality when infected with Among adult patients with and positive influenza rapid the use of a for was not associated with viral time to resolution of influenza illness or clinical compared with the following elegant by the importance of the and the of and such as and suggest that similar studies be performed with or other of such as timely antibiotic and determine outcome from have reduced of and at compared with leading to of a of increased mortality from common diseases. et this in a database and showed that from 23 patients with severe CAP, was associated with a increase in mortality for to quality of care was suggested by a lower frequency of microbiological but the data set was not to into other markers of quality of These data are similar in many but are controversial of the different characteristics of patients at and the risk of et evaluated the predictors of in patients with CAP and in of The authors performed a study in CAP patients with and identified that patients to at in the hospital and require at of The most common pathogen was and of the patients hospital was associated with lower pathogen identification and a of an but further studies are need to this the past there were two contributions to the journal in the area of The to the presented from on patients by et The authors the characteristics of and to determine tuberculosis in this of They identified patients without previous of with of receiving therapy and a with low viral The results showed between positive and were no between and viral with positive were for and and lower in with no with or viral than of the positive and results to negative during the of these the case of tuberculosis observed of The authors that the results found in and the of these to identify patients in In addition, it that at patients in tuberculosis may and further for the management et tested as a and immune response is a of of from the of the is as a of and to the mechanism of The authors used an in infection to whether tuberculosis The authors found that was in and primary They also found that was an of and and these in of Therefore, to present properties against infection in but further and studies are in order to patients at risk for Several the clinical the clinical outcomes and the treatment of NTM infections. 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