Diego J. Maselli

Lung transplant infection.

Lung transplantation has become an accepted therapeutic procedure for the treatment of end‐stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection‐ and rejection‐related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed.

Management of asthma during pregnancy

Asthma is an inflammatory lung condition that is the most common chronic disease affecting pregnancy. The changes in pulmonary physiology during pregnancy include increased minute ventilation, decreased functional residual capacity, increased mucus production, and airway mucosa hyperemia and edema. Pregnancy is also associated with a physiological suppression of the immune system. Many studies have described the heterogeneous immune system response in women with asthma during pregnancy, which partly explains why asthma has been shown to worsen, improve, or remain stable in equal proportions of women during pregnancy. Asthma may be associated with poor maternal and fetal outcomes. However, better maternal and fetal outcomes are observed with better asthma control. Asthma controller medications are generally thought to be safe during pregnancy, but limited data are available for some of the medicines. Newer medications like omalizumab open avenues for the treatment of asthma, but also pose a challenge, as there is limited experience with their use. Therefore, a multidisciplinary approach, including obstetricians, asthma specialists, and pediatricians should collaborate with the patient to carefully weigh the risks and benefits to determine an optimal management plan for each individual patient. The aim of this review article is to summarize the most recent literature about the immunological changes that occur during pregnancy, physiological and clinical implications of asthma on pregnancy, and asthma management and medication use in pregnant women.

Safety of β-blockers in the acute management of cocaine-associated chest pain.

BACKGROUND Cocaine is the most commonly abused illegal drug in patients presenting to emergency departments (EDs) because of chest pain and accounts for almost 40% of all drug-related visits. It is not known whether all β-blockers (BB) and β1-selective agents or mixed α1/β-adrenergic antagonists (α1/β-BB) are safe in the acute management of cocaine-associated chest pain, due to concerns of unopposed α-receptor activity resulting in coronary artery spasm and hypertensive urgency. METHODS Patients who presented to the EDs of 2 large inner city hospitals because of chest pain and who tested positive for cocaine were identified by retrospective chart review. Demographic characteristics, symptoms, vital signs, electrocardiographic abnormalities, medication use, comorbidities, and troponin values were documented. The presence and type of BB used were studied in relation to peak elevation in troponin T and troponin I. Troponin elevation was defined as a troponin I greater than 0.6 ng/mL and troponin T greater than 0.1 ng/mL if serum creatinine was less than 2 mg/dL. RESULTS A total of 378 patients were included in the study; of these, 78% (n = 296) were black; 12% (n = 44), white; and 10% (n = 38), of other race. Twelve percent (n = 46) of the patients had typical chest pain, 22% (n = 84) had coronary artery disease, 56% (n = 213) had hypertension, and 21% (n = 79) had diabetes mellitus. The admission electrocardiogram showed changes (ST elevation, ST depression, or T-wave inversion) in 43% (n = 163) of the patients. β-Blockers were used in 43% (n = 162) of the encounters. Troponin elevation occurred in 11% (n = 42) of patients. There was no difference in the number of patients with troponin rise in the BB and non-BB groups, 22 of 162 vs 20 of 213 (P = .2). There was no difference in mean peak troponin levels in patients with troponin rise who were treated with BB vs no BB, 6.7 vs 5.7 ng/mL (P = .6). There was no difference in mean peak troponin levels in patients with troponin rise who were treated with a β1-selective agents vs a α1/β-BB, 7.5 vs 4.1 ng/mL (P = .4). No cases of hypertensive urgency were identified after taking any BB. CONCLUSION Troponin rise is not uncommon in patients with cocaine-associated chest pain and occurred in 11% of the patients. In patients with cocaine-associated chest pain, BBs did not appear to change the incidence of troponin rise. β1-Selective BBs did not appear to worsen troponin levels compared with mixed α1/β-BB.

Risk factors and antibiotic therapy in P. aeruginosa community-acquired pneumonia.

Current guidelines recommend empirical treatment against Pseudomonas aeruginosa in community‐acquired pneumonia (CAP) patients with specific risk factors. However, evidence to support these recommendations is limited. We evaluate the risk factors and the impact of antimicrobial therapy in patients hospitalized with CAP due to P. aeruginosa.

Strategies in the prevention of ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) remains a significant problem in the hospital setting, with very high morbidity, mortality, and cost. We performed an evidence-based review of the literature focusing on clinically relevant pharmacological and nonpharmacological interventions to prevent VAP. Owing to the importance of this condition the implementation of preventive measures is paramount in the care of mechanically ventilated patients. There is evidence that these measures decrease the incidence of VAP and improve outcomes in the intensive care unit. A multidisciplinary approach, continued education, and ventilator protocols ensure the implementation of these measures. Future research will continue to investigate cost/benefit relationships, antibiotic resistance, as well as newer technologies to prevent contamination and aspiration in mechanically ventilated patients.

Efficacy of omalizumab in asthmatic patients with IgE levels above 700 IU/mL: a retrospective study

BACKGROUND Omalizumab is approved for patients with poorly controlled asthma with serum IgE levels between 30 and 700 IU/mL and positive test results for perennial allergens. Its efficacy in patients with IgE levels greater than 700 IU/mL is unclear. OBJECTIVE To evaluate the response of asthmatic patients treated with omalizumab with IgE levels greater than 700 IU/mL. METHODS Asthmatic patients treated with omalizumab for 6 months or longer with elevated IgE levels were evaluated retrospectively. Emergency department (ED) visits, hospitalizations, change in forced expiratory volume in 1 second, corticosteroid bursts, and Asthma Control Test (ACT) scores were recorded for a period of 6 months before and after treatment. RESULTS Twenty-six patients with an IgE level greater than 700 IU/mL (group 1) were matched by age, sex, and severity of asthma to patients with an IgE of 30 to 700 IU/mL (group 2). The mean numbers of ED visits before and after treatment were 0.96 vs 0.23 (P = .008) in group 1 and 0.65 vs 015 (P = .02) in group 2. Both group 1 and group 2 had an improvement in asthma control based on the mean ACT score before and after treatment (15.6 vs 18.9 [P = .02] and 15.4 vs 19 [P = .006], respectively). There was also a significant reduction in the frequency of systemic corticosteroid use during the 6 months before and after treatment (2.58 vs 0.96 [P < .001] and 2.62 vs 1.23 [P < .001] systemic steroid treatments, respectively). CONCLUSION Omalizumab was as effective in reducing ED visits, controlling asthma symptoms, and reducing the need for systemic corticosteroids in patients with IgE levels greater than 700 IU/mL compared with patients with levels of 30 to 700 IU/mL.

Clinical evaluation of the role of ceftaroline in the management of community acquired bacterial pneumonia

Ceftaroline fosamil (ceftaroline) was recently approved for the treatment of community- acquired pneumonia (CAP) and complicated skin infections. This newly developed cephalosporin possesses a broad spectrum of activity against gram-positive and gram-negative bacteria. Most importantly, ceftaroline demonstrates potent in vitro antimicrobial activity against multi-drug resistant Streptococcus pneumoniae and methicillin-resistant strains of Staphylococcus aureus. In two Phase III, double-blinded, randomized, prospective trials (FOCUS 1 and FOCUS 2), ceftaroline was shown to be non-inferior to ceftriaxone for the treatment of CAP in hospitalized patients. Ceftaroline exhibits low resistance rates and a safety profile similar to that of other cephalosporins. In this review, we will evaluate the pharmacological characteristics, safety, antimicrobial properties, and efficacy of ceftaroline and its applications in the treatment of CAP.

Incidence and aetiologies of pulmonary granulomatous inflammation: A decade of experience

Granulomatous lung disease (GLD) is caused by a wide range of conditions. Often there is a need to correlate pathological findings with clinical, microbiological or radiological data to determine an aetiology. The aim of this study was to determine the different aetiologies of GLD over the past decade.

Impact of Macrolide Therapy in Patients Hospitalized With Pseudomonas aeruginosa Community-Acquired Pneumonia

BACKGROUND Several studies have described a clinical benefit of macrolides due to their immunomodulatory properties in various respiratory diseases. We aimed to assess the effect of macrolide therapy on mortality in patients hospitalized for Pseudomonas aeruginosa community-acquired pneumonia (CAP). METHODS We performed a retrospective population-based study of > 150 hospitals in the US Veterans Health Administration. Patients were included if they had a diagnosis of CAP and P aeruginosa was identified as the causative pathogen. Patients with health-care-associated pneumonia and immunosuppression were excluded. Macrolide therapy was considered when administered within the first 48 h of admission. Univariate and multivariable analyses were performed using 30-day mortality as the dependent measure. RESULTS We included 402 patients with P aeruginosa CAP, of whom 171 (42.5%) received a macrolide during the first 48 h of admission. These patients were older and white. Macrolide use was not associated with lower 30-day mortality (hazard ratio, 1.14; 95% CI, 0.70-1.83; P = .5). In addition, patients treated with macrolides had no differences in ICU admission, use of mechanical ventilation, use of vasopressors, and length of stay (LOS) compared with patients not treated with macrolides. A subgroup analysis among patients with P aeruginosa CAP in the ICU showed no differences in baseline characteristics and outcomes. CONCLUSIONS Macrolide therapy in the first 48 h of admission is not associated with decreased 30-day mortality, ICU admission, need for mechanical ventilation, and LOS in hospitalized patients with P aeruginosa CAP. Larger cohort studies should address the benefit of macrolides as immunomodulators in patients with P aeruginosa CAP.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.