Pulmonary hypertension (PH) may complicate idiopathic pulmonary fibrosis (IPF) but the prevalence of PH in IPF remains undefined. The present authors sought to describe the prevalence of PH in IPF.The lung transplant registry for the USA (January 1995 to June 2004) was analysed and IPF patients who had undergone right heart catheterisation (RHC) were identified. PH was defined as a mean pulmonary arterial pressure (P̄_pa) ≥25 mmHg and severe PH as aP̄_pa>40 mmHg. Independent factors associated with PH were determined.Of the 3,457 persons listed, 2,525 (73.0%) had undergone RHC. PH affected 46.1% of subjects; ∼9% had severe PH. Variables independently associated with mild-to-moderate PH were as follows: need for oxygen, pulmonary capillary wedge pressure (P_pcw) and forced expiratory volume in one second (FEV₁). Independent factors related to severe PH included the following: carbon dioxide tension, age, FEV₁,P_pcw, need for oxygen and ethnicity. A sensitivity analysis in subjects withP_pcw<15 mmHg did not appreciably alter the present findings.Pulmonary hypertension is common in idiopathic pulmonary fibrosis patients awaiting lung transplant, but the elevations in mean pulmonary arterial pressure are moderate. Lung volumes alone do not explain the pulmonary hypertension. Given the prevalence of pulmonary hypertension and its relationship with surrogate markers for quality of life (e.g.activities of daily living), future trials of therapies for this may be warranted.

Pulmonary hypertension (PH) is a predictor of poor outcome in sarcoidosis. Little is known about the epidemiology of PH in sarcoidosis.The current authors reviewed the records of patients with sarcoidosis listed for lung transplantation in the USA between January 1995 and December 2002. PH was defined as a mean pulmonary artery pressure of >25 mmHg and severe PH as a mean pulmonary artery pressure of ≥40 mmHg.The cohort included 363 patients of whom 73.8% had PH. Neither spirometric testing nor the need for corticosteroids was associated with PH. Subjects with PH required more supplemental oxygen (2.7±1.8 L·min⁻¹versus1.6±1.4 L·min⁻¹). The cardiac index was lower in individuals with PH, whereas the pulmonary capillary wedge pressure was higher. In multivariate analysis, supplemental oxygen remained an independent predictor of PH, whereas the relationship between cardiac index and PH was no longer significant. As a screening test, the need for oxygen had a sensitivity and specificity of 91.8% and 32.6%, respectively.Pulmonary hypertension is common in advanced sarcoidosis. The need for oxygen correlates with pulmonary hypertension. Since pulmonary hypertension is associated with poor outcomes and because simple clinical criteria fail to identify patients with sarcoidosis and pulmonary hypertension, more aggressive screening for this should be considered.

Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. We conducted a retrospective cohort study in Premier Perspective database (2009–2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/−15.3 vs. 69.1+/−15.9 years, p < 0.001), and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those with non-CRE. Both chronic (Charlson score 2.0+/−2.0 vs. 1.9+/−2.1, p = 0.009) and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation 35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE subjects, respectively. CRE patients were 3× more likely to receive IET than non-CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of 5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95% confidence interval $9497, $11,126, p < 0.001) in costs. In this large US database, the prevalence of CRE among patients with Enterobacteriaceae UTI, pneumonia or sepsis was comparable to other national estimates. Infection with CRE was associated with a four-fold increased risk of receiving IET, which in turn increased mortality, LOS and costs.

Research from JAMA — Acute Eosinophilic Pneumonia Among US Military Personnel Deployed in or Near Iraq — ContextAcute eosinophilic pneumonia (AEP) is a rare disease of unknown etiology characterized by respiratory failure, radiographic infiltrates, and eosinophilic infiltration of the lung.ObjectivesTo describe a case series of AEP, illustrate the clinical features of this syndrome, and report the results of an epidemiologic investigation.Design, Setting, and ParticipantsEpidemiologic investigation of cases of AEP identified both retrospectively and prospectively from March 2003 through March 2004 among US military personnel deployed in or near Iraq. Survivors were offered a follow-up evaluation.Main Outcome MeasureMorbidity and mortality related to AEP.ResultsThere were 18 cases of AEP identified among 183 000 military personnel deployed in or near Iraq during the study period, yielding an AEP incidence of 9.1 per 100 000 person-years (95% confidence interval, 4.3-13.3). The majority of patients (89%) were men and the median age was 22 (range, 19-47) years. All patients used tobacco, with 78% recently beginning to smoke. All but 1 reported significant exposure to fine airborne sand or dust. Known causes of pulmonary eosinophilia (eg, drug exposures or parasitic disease) were not identified. Epidemiologic investigation revealed no evidence of a common source exposure, temporal or geographic clustering, person-to-person transmission, or an association with recent vaccination. Six patients underwent bronchoalveolar lavage (median eosinophilia of 40.5%). All patients developed peripheral eosinophilia (range, 8%-42%). Mechanical ventilation was required in 67% for a median of 7 (range, 2-16) days. Two soldiers died; the remainder responded to corticosteroids and/or supportive care. Twelve individuals were reevaluated a median of 3 months after diagnosis. At that point, 3 patients reported mild dyspnea and 1 reported wheezing. All patients had finished treatment and had either normal or nearly normal spirometry results. None had recurrent eosinophilia.ConclusionsAEP occurred at an increased rate among this deployed military population and resulted in 2 deaths. Failure to consider AEP in the differential diagnosis of respiratory failure in military personnel can result in missing this syndrome and possibly death. The etiology of AEP remains unclear, but the association with new-onset smoking suggests a possible link.

Research from JAMA Internal Medicine — Prediction of Infection Due to Antibiotic-Resistant Bacteria by Select Risk Factors for Health Care–Associated Pneumonia

Introduction Improved methods to optimize drug dosing in the critically ill are urgently needed. Traditional prescribing culture involves recognition of factors that mandate dose reduction (such as renal impairment), although optimizing drug exposure, through more frequent or augmented dosing, represents an evolving strategy. Elevated creatinine clearance (CL_CR) has been associated with sub-therapeutic antibacterial concentrations in the critically ill, a concept termed augmented renal clearance (ARC). We aimed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients, while also examining demographic, physiological and illness severity characteristics that may help identify this phenomenon. Methods This prospective observational study was performed in a 30-bed tertiary level, university affiliated, adult intensive care unit. Consecutive traumatized and septic critically ill patients, receiving antibacterial therapy, with a plasma creatinine concentration ≤110 μmol/L, were eligible for enrolment. Pulse contour analysis (Vigileo / Flo Trac^® system, Edwards Lifesciences, Irvine, CA, USA), was used to provide continuous cardiac index (CI) assessment over a single six-hour dosing interval. Urinary CL_CR measures were obtained concurrently. Results Seventy-one patients contributed data (sepsis n = 43, multi-trauma n = 28). Overall, 57.7% of the cohort manifested ARC, although there was a greater prevalence in trauma (85.7% versus 39.5%, P <0.001). In all patients, a weak correlation was noted between CI and CL_CR (r = 0.346, P = 0.003). This was mostly driven by septic patients (r = 0.508, P = 0.001), as no correlation (r = -0.012, P = 0.951) was identified in trauma. Those manifesting ARC were younger (P<0.001), male (P = 0.012), with lower acute physiology and chronic health evaluation (APACHE) II (P= 0.008) and modified sequential organ failure assessment (SOFA) scores (P = 0.013), and higher cardiac indices (P = 0.013). In multivariate analysis, age ≤50 years, trauma, and a modified SOFA score ≤4, were identified as significant risk factors. These had greater utility in predicting ARC, compared with CI assessment alone. Conclusions Diagnosis, illness severity and age, are likely to significantly influence renal drug elimination in the critically ill, and must be regularly considered in future study design and daily prescribing practice. See related commentary by De Waele and Carlier, http://ccforum.com/content/17/2/130