John G. Armstrong

SMART-COP: A Tool for Predicting the Need for Intensive Respiratory or Vasopressor Support in Community-Acquired Pneumonia

BACKGROUND Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

The Etiology of Community-Acquired Pneumonia in Australia: Why Penicillin plus Doxycycline or a Macrolide Is the Most Appropriate Therapy

BACKGROUND Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. METHODS The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. RESULTS The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. CONCLUSIONS The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Alveolar haemorrhage in anti‐glomerular basement membrane disease without detectable antibodies by conventional assays

Anti-glomerular basement membrane (anti-GBM) disease represents the spectrum of disease attributable to circulating anti-GBM antibodies. While active anti-GBM disease in the absence of circulating anti-GBM antibodies has been described, it is considered rare with the use of current routinely available assays. We report four subjects with features consistent with active anti-GBM antibody disease without detectable antibodies by routinely available enzyme linked immunosorbent assay (ELISA) and immunoblot techniques. All were smokers who presented with diffuse alveolar haemorrhage, minimal renal involvement, and undetectable anti-GBM antibodies. Seronegative anti-GBM disease with predominant pulmonary involvement may be more common than previously appreciated and should be part of the differential diagnosis for otherwise unexplained diffuse alveolar haemorrhage. Renal biopsy with immunofluorescent studies should be considered in the diagnostic evaluation of such subjects, including those with idiopathic pulmonary haemosiderosis.

Diffuse alveolar haemorrhage in a young male smoker: a word of caution

We read with interest Corte and Tattersall’s report in this journal of a case of diffuse alveolar haemorrhage (DAH), which was ascribed the diagnosis of ‘idiopathic pulmonary haemosiderosis’ (IPH). We wonder how confidently antiglomerular basement membrane (anti-GBM) disease was excluded in this case? There have been several reported cases of ‘IPH’ subsequently shown to be unrecognized antiGBMdisease, withmisdiagnosis resulting from an apparent lack of renal involvement at initial presentation. Unfortunately, histopathology of lung tissue from patients with anti-GBM disease is not specific for this disease and the serum levels of circulating anti-GBM antibodies may be below the detection limit of conventional and routinely available assays (namely ELISA, immunoblot and indirect immunofluorescence). It is possible that ‘IPH’ may actually represent a form fruste of anti-GBM disease, at least in a subset of cases. Indeed, Salama et al. have recently described a novel highly sensitive biosensor assay that was able to detect circulating anti-GBM antibodies in patients who were considered as ‘anti-GBM negative’ by conventional assays. In a young adult male smoker with apparently isolated DAH, we would be hesitant in confidently diagnosing ‘IPH’ in the absence of strongly negative evidence such as renal histopathology. Although not routinely available in Australia or New Zealand, the future availability of the more sensitive biosensor assay may also be helpful. If the available clinical evidence argues against pursuing more aggressive diagnostic techniques, including renal biopsy (as in the case reported by Corte and Tattersall), then close monitoring for the development of renal disease is recommended, in addition to counselling this patient strongly against continued cigarette smoking.

E-4. Radiation therapy of lung cancer detected by screening

Spiral CT scan screening for lung cancer may diagnose a large volume of patients with early stage cancers, potentially curable with local treatment alone. Surgery is likely to be the usually offered treatment. However, some patients present with surgically resectable disease have medical contraindications or refuse surgery [l]. For such patients, primary radiation therapy offers an alternative and potentially curative approach. The very good results reported with surgery for early stage disease may in part be due to the more favorable performance status of surgical patients and the fact that surgically treated patients are more rigorously staged and the results are reported by pathological stage rather than clinical stage. Most patients who receive primary radiation therapy are not surgically staged and may have occult N2 (mediastinal) disease, whereas such patients may be excluded or reported separately in surgical series. Results of radiation alone for medically inoperable early stage lung cancer: There are many series which document reasonable survival following radical radiation alone for stage I and II cancers. [2-61 While 5-year survival from all causes may be low, the cause specific survival is often substantially higher due to high rates of intercurrent illnesses. Cause specific survival ranges from 20-50% at 5 years.[7,8] Locoregional failure (using traditional radiologic and clinical criteria) is the dominant cause of failure ranging from approximately 40-50%. [8,9] This may underestimate of local failure as traditional clinical/radiologic assessment of local failure following radiation nderestimates the incidence in locally advanced cancer. In one series routine bronchoscopy was performed during follow-up, and local control was less than 20% at 1 year. [IO] There is clearly a need to improve the locoregional disease eradication rates to impact on survival. This could be achieved by better patient selection and improved radiation technology. Patient selection: PET is an expensive imaging technique which requires the availability of a cyclotron and is not, therefore, widely available. Reports have demonstrated accuracy rates of 80-100% in the detection of nodal metastases compared to approximately 65% for CT and MRI (151. PET also has the advantage of providing accurate whole body staging. PET can also e used in helping to refine the process of radiation target volume delineation. The advent of accurate non-invasive staging with PET could have as substantial impact on the use of radiation for this category of patients by removing advanced stage patients from the series of the future. Radiation pulmonary toxicity could contribute to increased morbidity and even mortality. It would be useful to exclude patients in whom the treatment would be more likely to cause damage than improve survival. There are no strict guidelines for such selection, however it may be possible to identify patients likely to have very poor pulmonary function post-radiation in a manner analogous to the preoperative selection of patients. Investigators at the NKI calculate the FEVl post-RT to be:

Chemoradiation for inoperable non small cell lung cancer: A phase II study using a regimen with acceptable toxicity

Over the past few years there have been numerous schedules of combined modality therapy proposed as being useful in the management of inoperable non-small cell lung cancer (NSCLC). These have generally involved the use of high dose radiation therapy to doses of the order of 60 Gy combined with chemotherapy given prior to or concurrently with the radiation. Concurrent chemotherapy has been given with the intention of being both active in NSCLC and with the role of being a possible radiosensitiser. The most commonly employed drugs have been cisplatin, etoposide, 5-fluorouracil, vindesine and mitomycin. Although response rates of the primary tumour to the combined therapy have been optimistic, there has not been a great survival benefit with the median survival in most series remaining at just over 12 months. In this study we have prospectively treated a group of patients with non-metastatic inoperable NSCLC with a regimen of known acceptable toxicity. These patients were inoperable because they were unfit for surgery or had locally advanced disease. The local radiological response rate was 86% and the median survival for the whole group was 13 months. Adenocarcinomas appeared to do significantly worse than squamous cell carcinomas. Toxicity was acceptable and lower than reported in other similar series. There was one treatment related death. We feel that this combination of radiation therapy and chemotherapy is a reasonable compromise for a disease which still has a very poor outlook.